Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.94361721 |
In this report , a rat trk protooncogene cDNA has been isolated from PC 12 cells and Trk has been shown to bind NGF , generating a complex of 158 kDa . 0.94361721^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.54590553 |
NGF interacts with the protein product of the proto oncogene trk and rapidly stimulates the tyrosine phosphorylation of both p140prototrk and a number of cellular substrates . 0.54590553^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.52430222 |
NGF binds to both trkA , a tyrosine kinase receptor , and to the p 75 nerve growth factor receptor , a protein lacking a consensus signalling sequence . 0.52430222^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.590982 |
Several lines of evidence suggest that NGF is also the ligand for trkE ; ( 1 ) normal human keratinocytes bind NGF with high affinity , ( 2 ) NGF stimulates keratinocyte growth in an autocrine fashion , ( 3 ) NGF exerts its biological effect on keratinocytes through the stimulation of a trk specific tyrosine kinase , and ( 4 ) keratinocytes lack trkA but do express large amount of trkE . trkE might also be the NGF receptor by other human peripheral tissues , such as pancreatic islets , and might represent a non neuronal receptor for this ligand . . 0.590982^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.65438835 |
Interaction of the nerve growth factor ( NGF ) receptor / Trk with cellular substrates was investigated by transient co overexpression in human 293 fibroblasts using ET R , a chimeric receptor consisting of the epidermal growth factor receptor ( EGF R ) extracellular ligand binding domain and the Trk transmembrane and intracellular signal generating sequences . 0.65438835^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.61983603 |
NGF binds with high affinity to the extracellular region of the tyrosine kinase receptor TrkA . 0.61983603^^^ |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.55140808 |
To clarify the role of the common neurotrophin receptor p 75 in modulating the survival response of sensory and sympathetic neurons to NGF at different stages of development , we compared the actions of wild type NGF with a mutated NGF protein that binds normally to TrkA , the NGF receptor tyrosine kinase , but has greatly reduced binding to p 75 . 0.55140808^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.56138577 |
NGF binds to the TrkA tyrosine kinase and the p 75 neurotrophin receptor , a member of the tumor necrosis factor cytokine family . 0.56138577^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.8686553 |
Interaction between NGF and TrkA RED was also demonstrated by size exclusion chromatography , light scattering , and chemical crosslinking with evidence for formation of a higher molecular weight complex consistent with a ( TrkA RED ) 2 ( NGF dimer ) complex . 0.8686553^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.62452101 |
NGF binds to TrkA , activates the intrinsic kinase activity of TrkA , and promotes the differentiation of pheochromocytoma ( PC 12 ) cells into sympathetic like neurons . 0.62452101^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.58774767 |
Thus , CHK is a novel signaling molecule that participates in TrkA signaling , associates directly with TrkA receptors upon NGF stimulation , and is involved in neurite outgrowth of PC 12 cells in response to NGF . . 0.58774767^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.52814442 |
Especially in the absence of NGF , 5HT alpha ( 2 ) M was found to bind to TrkA ( the high affinity receptor for NGF ) much better than normal alpha ( 2 ) M ( N alpha ( 2 ) M ) . 5HT alpha ( 2 ) M dose dependently inhibited NGF promoted autophosphorylation of TrkA , and decreased the expression of two immediate early genes ( NGFI A and c jun ) and two delayed response genes ( SCG 10 and transin ) which are associated with neurite outgrowth in PC 12 cells . 0.52814442^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.71137331 |
NGF binds with high affinity to the extracellular region of a tyrosine kinase receptor , TrkA , which comprises three leucine rich motifs ( LRMs ) , flanked by two cysteine rich clusters , followed by two immunoglobulin like ( Ig like ) domains . 0.71137331^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.51973816 |
NGF binds to its receptor trkA on terminal axons and signals the neuron cell body in the ganglion . 0.51973816^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.98127902 |
The current hypothesis is that NGF bound to TrkA at the axon terminal is internalized into signaling endosomes , with NGF in their lumens bound to phosphorylated TrkA in their membranes , which are retrogradely transported to the cell bodies , where TrkA activates downstream signaling molecules that promote neuronal survival and regulate many aspects of neuronal gene expression . 0.98127902^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Multiple trkA proteins in PC 12 cells bind NGF with a slow association rate . ^^^ All trkA bands were phosphorylated on tyrosine residues when bound to mNGF , suggesting that they participate in NGF induced signal transduction . ^^^ NGF binding kinetics to all three trkA bands were indistinguishable , with slow dissociation rates , and a slow association rate that required approximately 1 h to reach equilibrium levels at 4 degrees C . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Monoclonal anti NGF antibodies that specifically inhibit the biological activity of mouse beta NGF were used to study the structural determinants involved in the interaction of NGF with its receptors gp75LNGFR and Trk . ^^^ Only the gamma subunit inhibited phosphorylation of Trk and biological activity of beta NGF . ^^^ The region encompassing the N terminus , the C terminus , and the loop on the surface of beta NGF containing residues 60 80 is proposed as important for binding to the Trk receptor . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immunoblots of homogenates from human tumors displayed binding of anti nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , and NT 3 antibodies as well as of anti tyrosine specific protein kinase ( Trk ) A , TrkB , and TrkC receptor antibodies , with similar migration characteristics than those displayed by human beta NGF and proteins from rat brain . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Retrovirus mediated transfer of the beta NGF gene into NET cells activated TrkA and consistently decreased their proliferative responses to insulin like growth factor ( IGF ) 1 , IGF 2 , fibroblast growth factor 2 , and epidermal growth factor ( EGF ) , down regulating EGF and IGF 1 binding sites . ^^^ |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These data indicate that a gene ( or genes ) other than TRKA is probably responsible for HSAN 5 in some patients . . ^^^ |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Ras was not required for NGF induced activation of Trk or tyrosine phosphorylation of PLC gamma 1 . ^^^ |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In this report , we demonstrate that K252a is a potent inhibitor ( IC 50 of 3 nM ) of the tyrosine protein kinase activity of the NGF receptor gp140trk , the product of the trk protooncogene . ^^^ |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
They are apparently composed of two membrane bound proteins , p 75 and the protooncogene trk , both of which bind NGF , and apparently contribute singularly or in concert to the two observed affinities , and to the promotion of the NGF effects . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Concentrations of 10 100 nM staurosporine and K252A inhibit NGF dependent tyrosine phosphorylation in PC 12 cells and inhibit trk oncogene dependent tyrosine phosphorylation in trk transformed NIH3T3 ( trk 3T3 cells ) . ^^^ NGF stimulated tyrosine phosphorylation of the pp140c trk NGF receptor and tyrosine phosphorylation of pp70trk are also inhibited by similar concentrations of staurosporine and K252A , whereas tyrosine phosphorylation of the EGF receptor , insulin receptor , and 5 src is not affected . ^^^ These data suggest that staurosporine and K252A specifically inhibit the trk tyrosine kinase activity through a direct mechanism , probably accounting for the attenuation by these agents of the cellular actions of NGF . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Disruption of the low affinity receptor binding site in NGF allows neuronal survival and differentiation by binding to the trk gene product . ^^^ The product of the proto oncogene trk , p140trk , is a tyrosine kinase receptor that has been identified as a signal transducing receptor for NGF , while the role of the low affinity NGF receptor , p75NGFR , in signal transduction is less clear . ^^^ |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Tyrosine kinase receptor ( trk ) mRNA encoding an essential component of the high affinity NGF receptor was also present at all stages . ^^^ |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) binds to a specific cell surface receptor ( NGFR ) that exists in high affinity ( now called trk ) and low affinity ( now called p75NGFR ) forms . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The other is one of a family of tyrosine kinase receptors trkA binds only NGF , the related trkB receptor binds BDNF and NT 3 , and trkC binds NT 3 alone . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The cellular localization of mRNAs encoding the low affinity NGF receptor ( here referred to as LANR ) and the putative high affinity receptor for NGF , trk , have been studied in the human foetal spinal and sympathetic ganglia , and spinal cord , using in situ hybridization . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
A 140 K tyrosine protein kinase encoded by the proto oncogene trk has been found to bind NGF with high affinity ( Kd of 10 ( 11 ) M ) and to evoke the cellular neurotrophic responses . ^^^ The expression of trk and LNGFR mRNA are co localized in the rat brain to the medial septal nucleus and the nucleus of Broca ' s diagonal band containing the NGF responsive magnocellular cholinergic neurons projecting to hippocampus and cerebral cortex . ^^^ This region could be altered , resulting in the total loss of LNGFR binding by the mutant NGF protein without affecting the binding to the trk receptor which was sufficient for the full biological activity . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Since NGF activates the tyrosine kinase activity of gp140trk , the protein product of the trk proto oncogene , we also examined the association of PtdIns 3 kinase with gp140trk . ^^^ |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The second NGF receptor is a member of the trk family of tyrosine kinase receptors , p140trkA . ^^^ |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The activation of this enzyme by growth factors is evaluated in PC 12 pheochromocytoma cells and NIH 3T3 fibroblasts expressing the pp140c trk nerve growth factor ( NGF ) receptor ( 3T3 c trk ) . ^^^ NGF causes the rapid stimulation of PI 3 kinase activity detected in anti phosphotyrosine , but not in anti trk , immunoprecipitates . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) binds to two structurally unrelated transmembrane proteins on the surface of PC 12 cells , a 75 kDa glycoprotein with a short cytoplasmic sequence , and the trk protooncogene ( pp140c trk ) , a protein tyrosine kinase activated by NGF . ^^^ Expression of pp140c trk in 3T3 fibroblasts ( 3T3 c trk ) , as evidenced by cross linking of 125I NGF to the 140 kDa protein , permits the NGF dependent activation of raf 1 kinase , detected in the immunoprecipitate kinase assay , anti raf immunoblot shift on gel electrophoresis , and incorporation of [ 32P ] orthophosphate into the raf 1 protein . ^^^ The concentration dependence of raf 1 activation is identical in 3T3 c trk and PC 12 cells , despite the absence of the 75 kDa NGF binding protein in 3T3 c trk cells . ^^^ Similarly , the NGF dependent activation of mitogen activated protein ( MAP ) kinase is detected in 3T3 c trk cells , but not in untransfected 3T3 or Chinese hamster ovary cells overexpressing p 75 . ^^^ As described for raf 1 activation , the NGF dose responses for MAP kinase activation in 3T3 c trk and PC 12 cells are virtually superimposable . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Exposure to RA leads neither to an increase in the expression of mRNA for trk , another component of the NGF receptor , nor to an increase in binding to high affinity receptors , suggesting that an increase in the expression of p75NGFR is sufficient to make cells more sensitive to NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
All tissues examined coexpressed the low affinity NGF receptor ( LNGFR ) , whereas none of these tissues expressed the high affinity NGF receptor encoded by the trk protooncogene . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Whereas PC 12 cells elaborated neurites after 2 days of continuous exposure to NGF , PC 12 cells overexpressing gp140trk by 20 fold ( trk PC 12 ) began this process within hours . ^^^ Compared with wild type PC 12 cells , trk PC 12 exhibited an increase in both high and low affinity NGF binding sites . ^^^ Furthermore , trk PC 12 cells displayed an enhanced level of NGF dependent gp140trk autophosphorylation , and this activity was sustained for many hours following ligand binding . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Dorsal root ganglion neurons expressing trk are selectively sensitive to NGF deprivation in utero . ^^^ The recent identification of trk , trkB , and trkC as the putative high affinity receptors for NGF , brain derived neurotrophic factor , and neurotrophin 3 , respectively , has allowed an examination of whether their expression by DRG neurons correlates with differential sensitivity to immune deprivation of NGF . ^^^ In situ hybridization demonstrates that virtually all neurons expressing trk are lost during in utero NGF deprivation . ^^^ These experiments show that DRG neurons expressing trk require NGF for survival . ^^^ Finally , these experiments provide evidence that trk , and not p75NGFR , is the primary effector of NGF action in vivo . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The cellular actions of nerve growth factor ( NGF ) involve changes in protein phosphorylation , initiated by the binding and subsequent activation of its tyrosine kinase receptor , the trk protooncogene ( pp140c trk ) . ^^^ Upon exposure to NGF , a 38 kDa tyrosine phosphorylated protein ( pp 38 ) is identified in both PC 12 pheochromocytoma cells and NIH3T3 cells transfected with the full length human pp140c trk cDNA ( 3T3 c trk ) that is specifically coimmunoprecipitated with pp140c trk or phosphatidylinositol phospholipase C ( PLC ) gamma 1 . ^^^ In both PC 12 and 3T3 c trk cells , NGF rapidly stimulates the association of pp140c trk and pp 38 with a fusion protein containing the src homology ( SH ) domains of PLC gamma 1 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
RNA marks NGF responsive forebrain neurons : evidence that trk gene expression is induced by NGF . ^^^ Recent data indicate that the product of the trk gene , p140trk , is a critical component of the NGF receptor . ^^^ Furthermore , induction of trk expression by NGF suggests that neurotrophin mediated up regulation of their receptor tyrosine kinases is an important feature of their actions and that neurotrophins may regulate the activity of responsive neurons through increasing the level of their receptors . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In PC 12 cells that overexpressed the tyrosine kinase encoded by the trk proto oncogene ( a component of the high affinity NGF receptor ) , the NGF induced activation of the regulatory proteins was potentiated . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Recent data have demonstrated that the product of the tyrosine kinase trk proto oncogene binds NGF and is a component of the high affinity NGF receptor . ^^^ Thus , the trk family of receptors are likely to be important signal transducers of NGF related trophic signals in the formation and maintenance of neuronal circuits . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Colocalization of NGF binding sites , trk mRNA , and low affinity NGF receptor mRNA in primary sensory neurons : responses to injury and infusion of NGF . ^^^ The distributions of mRNAs for the protooncogene trk and the low affinity NGF receptor ( LNGFR ) were studied by hybridization with oligonucleotide probes on sections of adult rat primary sensory and sympathetic ganglia . ^^^ Among neurons in lumbar dorsal root ganglia and trigeminal ganglia , trk mRNA and NGF binding sites were closely colocalized ; this finding together with previous direct evidence in other cell types is taken to indicate that trk protein is an essential component of the high affinity NGF receptor in adult sensory neurons . ^^^ Following intrathecal infusion of NGF to otherwise normal dorsal root ganglia , the concentrations of LNGFR mRNA but not those of trk mRNA and NGF binding sites were increased in NGF responsive neurons . ^^^ Concentrations of NGF binding sites , LNGFR mRNA , and trk mRNA were all decreased by peripheral nerve transection and restored by exogenous NGF , the restoration being complete for LNGFR mRNA and partial for trk mRNA and NGF binding sites . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In cultures containing basal forebrain cholinergic neurons , but not in cultures of cerebral cortex , nerve growth factor ( NGF ) treatment for 4 min induced tyrosine phosphorylation of trk family proteins . ^^^ Our findings indicate involvement of trk receptor activation in the NGF response of basal forebrain cholinergic cells and provide evidence for widespread presence of BDNF and NT 3 responsive neurons in the embryonic brain . . ^^^ |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Induction of B Raf kinase activity in NGF treated PC 12 cells required expression of kinase active trk receptors . ^^^ |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The product of the trk proto oncogene encodes a receptor for nerve growth factor ( NGF ) . ^^^ These results indicate that the product of the trk proto oncogene is sufficient to mediate signal transduction processes induced by NGF and NT 3 , at least in proliferating cells . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These factors utilize the Trk family of receptor tyrosine kinases , perhaps in conjunction with a second component known as the low affinity NGF receptor ( LNGFR ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The trk proto oncogene rescues NGF responsiveness in mutant NGF nonresponsive PC 12 cell lines . ^^^ The trk tyrosine kinase proto oncogene product gp140prototrk binds nerve growth factor ( NGF ) and is rapidly and selectively activated by this neurotrophic factor . ^^^ PC12nnr cultures were transiently transfected with expression vectors encoding the full length rat trk cDNA and assessed for responsiveness to NGF . ^^^ Expression of exogenous trk rescued the capacity for NGF promoted neurite outgrowth , cellular hypertrophy , and serum free survival by these cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Messenger RNAs for trk and the low affinity NGF receptor in rat basal forebrain . ^^^ Recently , a 140 kDa tyrosine protein kinase encoded by the proto oncogene trk has been found to bind NGF with high affinity ( Kd of 10 ( 11 ) M ) and to evoke neurotrophic responses . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Tyrosine phosphorylation and tyrosine kinase activity of the trk proto oncogene product induced by NGF . ^^^ Here we show that NGF induces tyrosine phosphorylation and tyrosine kinase activity of the trk proto oncogene product , a tyrosine kinase receptor whose expression is restricted in vivo to neurons of the sensory spinal and cranial ganglia of neural crest origin . ^^^ Tyrosine phosphorylation of trk by NGF is rapid , specific and occurs with picomolar quantities of factor , indicating that the response is mediated by physiological amounts of NGF . ^^^ Activation of the trk tyrosine kinase receptor provides a possible mechanism for signal transduction by NGF . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Second , the protein tyrosine kinase encoded by the protooncogene trk ( p140trk ) , a member of the receptor class of tyrosine kinases , becomes activated and phosphorylated on tyrosine after NGF treatment of PC 12 cells [ Kaplan , D . ^^^ Our findings identify PLC gamma 1 as a likely substrate for the trk encoded tyrosine kinase , and they provide a link between NGF dependent activation of p140trk and the stimulation of intracellular second messenger pathways . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF induced tyrosine phosphorylation has been found to be initiated by the trk protooncogene , which participates in the formation of high affinity NGF binding sites . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Recent studies have demonstrated that the product of the trk proto oncogene , gp140trk , is the functional receptor for nerve growth factor ( NGF ) . ^^^ Finally , transfection of the trk proto oncogene into NGF non responsive PC 12 mutant cells restores NGF responsiveness . ^^^ These genes are highly related to the trk proto oncogene and encode tyrosine protein kinases which serve as functional receptors for the NGF related neurotrophins brain derived neurotrophic factor ( BDNF ) and neurotrophic 3 ( NT 3 ) , respectively . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In this study we show that the product of the human trk proto oncogene ( gp140trk ) binds NGF with high affinity . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Induction by NGF of meiotic maturation of Xenopus oocytes expressing the trk proto oncogene product . ^^^ The effect of nerve growth factor ( NGF ) was assessed in Xenopus oocytes expressing the human trk proto oncogene product , p140prototrk . ^^^ Thus the trk proto oncogene product can act as a receptor for NGF in a functionally productive manner . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
High affinity NGF binding requires coexpression of the trk proto oncogene and the low affinity NGF receptor . ^^^ Reconstitution experiments by membrane fusion and transient transfection into heterologous cells indicate that high affinity NGF binding requires coexpression and binding to both the low affinity NGF receptor and the tyrosine kinase trk gene product . ^^^ These studies reveal a new growth factor receptor mediated mechanism of cellular differentiation involving trk and the low affinity NGF receptor . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Pulsative stimulation of APUD cell carcinomas with NGF may therefore improve the response rate of these tumors to chemotherapy , which would be of significant clinical importance for patients with residual postoperative MTC tissue . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In PC 12 pheochromocytoma cells , exposure of [ 125I ] NGF followed by crosslinking indicates that the ligand binds to two discreet receptors , the previously described 75 kd protein , as well as the trk proto oncogene product pp140c trk . ^^^ Competition experiments reveal that of the two , pp 140c trk binds to NGF with higher affinity . ^^^ Following exposure to NGF , pp140c trk undergoes a rapid autophosphorylation on tyrosine residues , and concomitantly phosphorylates and associates with phospholipase C gamma 1 ( PLC gamma 1 ) , through interaction with its src homology domains . ^^^ The binding of NGF to pp140c trk with high affinity , the NGF dependent homology domains . ^^^ The binding of NGF to pp140c trk with high affinity , the NGF dependent activation of its tyrosine kinase activity and the specific association with the effector molecule , PLC gamma 1 , suggests that this is the biologically relevant signaling receptor for NGF . . ^^^ |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Furthermore , PC 12 mutants lacking the Trk NGF receptor tyrosine kinase also lack NGF inducible p21ras activation . ^^^ |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These compounds were also found to inhibit the binding of [ 125I ] NGF to its receptors in membranes from PC 12 cells ( which express p 75 as well as trka receptors for NGF ) and DG 44 CHO cells ( transfected with full length p 75 NGFR ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The Trk family of tyrosine protein kinases , TrkA , TrkB , and TrkC , are the signaling receptors that mediate the biological properties of the NGF family of neurotrophins . ^^^ In addition to the Trk receptors , the NGF family of neurotrophins also binds with low affinity to an unrelated molecule , designated p 75 , a member of the TNF receptor superfamily . ^^^ TrkA is the NGF receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The extracellular domains of the TrkA nerve growth factor ( NGF ) receptor and its homologs harbor a modular mosaic of potential ligand binding motifs , namely two immunoglobulin ( Ig ) like modules and an LRM 3 cassette consisting of a tandem array of three leucine rich motifs ( LRMs ) flanked by cysteine rich clusters ( Schneider , R . , and Schweiger , M . ( 1991 ) Oncogene 6 , 1807 1811 ) . ^^^ Further tracking down of this NGF binding site in TrkA strikingly revealed that a single LRM of 24 amino acids could bind NGF selectively with nanomolar affinity . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Methylamine activated alpha 2M ( MA alpha 2M ) and serotonin activated alpha 2M ( 5HT alpha 2M ) dose dependently inhibit NGF promoted neurite outgrowth of the pheochromocytoma PC 12 cell and its subline PC 12 ( 6 24 ) which overexpresses human trk protooncogene product , but have no effect on their viability , and this inhibition can be blocked by high concentrations of NGF . ^^^ The binding of MA alpha 2M to trk , which is a part of high affinity NGF receptor , was studied with PC 12 ( 6 24 ) cells and NIH 3T3 fibroblasts expressing trk ( trk 3T3 ) . ^^^ Both 5HT alpha 2M and MA alpha 2M also dose dependently block NGF promoted autophosphorylation of trk in vivo , whereas normal alpha 2M and plasmin reacted alpha 2M are inactive or much less active . ^^^ MA alpha 2M also blocks NGF promoted incorporation of 32P from [ 32P ] ATP into trk receptors in vitro . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
A Trk nerve growth factor ( NGF ) receptor point mutation affecting interaction with phospholipase C gamma 1 abolishes NGF promoted peripherin induction but not neurite outgrowth . ^^^ We analyzed the function of Trk nerve growth factor ( NGF ) receptors containing a point mutation ( Tyr > Phe ) in a major autophosphorylation site ( Tyr 785 ) . ^^^ Tyr 785 is required for phospholipase C gamma 1 to interact with Trk and to become tyrosine phosphorylated in response to NGF . ^^^ The altered receptors were transfected into a mutant subline of PC 12 rat pheochromocytoma cells ( designated PC12nnr5 ) that , unlike wild type PC 12 cells , lack expression of endogenous Trk and responsiveness to NGF . ^^^ PC12nnr5 cells permanently transfected with Trk Y785F exhibit NGF dependent autophosphorylation and normal NGF binding and internalization . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These results indicate that NGF and NT 3 act on functionally distinct populations of adult sensory neurons and suggest that a sizeable number of small DRG neurons may not respond to neurotrophins via a known Trk in the adult rat . . ^^^ |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Disruption of NGF binding to the low affinity neurotrophin receptor p75LNTR reduces NGF binding to TrkA on PC 12 cells . ^^^ Our results show that treatment of PC 12 cells with MC 192 , a monoclonal antibody directed against p75LNTR , results in reduced NGF binding to TrkA and attenuated TrkA activation . ^^^ Use of mutant NGF that binds TrkA but not p75LNTR shows that the MC 192 effect requires that NGF bind the p75LNTR receptor . ^^^ By preventing NGF binding to p75LNTR , NGF binding to TrkA and NGF mediated signal transduction were reduced . ^^^ We propose that p75LNTR normally acts to increase binding of NGF to TrkA , possibly by increasing the local NGF concentration in the microenvironment surrounding the cell surface TrkA receptor . . ^^^ |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) binds to two distinct cell surface receptors , TrkA , which is a receptor tyrosine kinase , and p75NGFR , whose role in NGF induced signal transduction remains unclear . ^^^ These results strongly suggest that NGF induced neuronal differentiation in IMR 32 cells is initiated through TrkA in the absence of p75NGFR . ^^^ |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The present data indicate that NGF may increase neuronal sensitivity to estrogen , and that estrogen , by differentially regulating p75NGFR and trkA mRNA , may alter the ratio of the two NGF receptors , and , consequently , neurotrophin responsivity . ^^^ |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
LNGFR regulates Trk signal transduction and NGF induced neuronal differentiation in MAH cells . ^^^ We have examined NGF induced signal transduction events and neuronal differentiation in MAH cells , a neuronal progenitor cell line , in which the expression of the two NGF receptors , p140trk ( Trk ) and p75LNGFR ( p 75 ) , has been independently manipulated . ^^^ Coexpression of a large molar excess of p 75 substantially enhances the NGF induced tyrosine autophosphorylation of Trk , compared with cells expressing Trk alone . ^^^ These biochemical and biological influences of p 75 are not observed using a mutant form of NGF that binds Trk but not p 75 . ^^^ These data provide evidence that p 75 can modulate signal transduction through Trk in a neuronal progenitor cell context and that such modulation has functional consequences for the neuronal differentiation pathway induced by NGF . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Mutation of only seven residues in NT 3 resulted in a human neurotrophin variant which bound to all receptors of the trk family with high affinity and efficiently supported the survival of NGF , BDNF and NT 3 dependent neurons . ^^^ We determined the binding sites of human neurotrophin 3 ( NT 3 ) to its receptors trkC and gp 75 by mutational analysis and compared them to the analogous interactions of nerve growth factor ( NGF ) with trkA and gp 75 . ^^^ A novel rapid biological screening procedure allowed the identification of NT 3 mutants that are able to signal efficiently through the non preferred receptors trkA and trkB , which are specific for NGF and BDNF respectively . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Retrograde axonal transport and lesion induced upregulation of the TrkA high affinity NGF receptor . ^^^ In this study we examined the distribution and transport of the TrkA NGF receptor using two anti peptide polyclonal antibodies and a monoclonal antibody , all of which are TrkA specific . ^^^ Thus , TrkA may itself be , or be a component of , the neurotrophic intraaxonal messenger by which NGF regulates gene expression in sensitive neurons . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Axonal transport of the trkA high affinity NGF receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This lack of influence of NGF on SOM is consistent with the absence of high affinity NGF receptors and trk mRNA in SOM positive neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To determine which neurotrophin may regulate the development of noradrenergic neurons in the chicken locus coeruleus , expression of trk receptors , retrograde transport of neurotrophins , and responses to NGF were examined . ^^^ Noradrenergic neurons in the locus coeruleus of birds express TrkA , transport NGF , and respond to NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Regulation of TrkA and ChAT expression in developing rat basal forebrain : evidence that both exogenous and endogenous NGF regulate differentiation of cholinergic neurons . ^^^ TrkA is a receptor tyrosine kinase whose activation transduces NGF signaling . ^^^ TrkA expression has been demonstrated in NGF responsive adult basal forebrain cholinergic neurons ( BFCNs ) . ^^^ We discovered that NGF administration in vivo activated TrkA receptors , and increased both TrkA and ChAT mRNA ; conversely , anti NGF infusions suppressed expression of both genes . ^^^ These results suggest that endogenous NGF regulates expression of TrkA and ChAT . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
All NGF stimulated tyrosine phosphorylation events were inhibited by preincubation of neurons with the tropomyosin related kinase ( trk ) inhibitor K252a . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA is a receptor tyrosine kinase for nerve growth factor ( NGF ) . ^^^ Recent studies indicate that NGF regulates not only activation of trkA kinase but also expression of the trkA gene . ^^^ To further define NGF actions on trkA , we examined binding and signaling through trkA after both short and long intervals of NGF treatment . ^^^ NGF appears to regulate trkA at several levels . ^^^ In neurons persistently exposed to NGF , maintenance of NGF signaling may require increased trkA gene expression . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The enhanced responsiveness to NGF in E 2 cells is not due to receptor overexpression as judged by TrkA protein levels and tyrosine kinase activity , but may be associated with the increased and prolonged tyrosine phosphorylation of ERK 1 ( extracellular signal regulated kinase 1 ) and ERK 2 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We report here that GM 1 directly and tightly associates with Trk , the high affinity tyrosine kinase type receptor for NGF , and strongly enhances neurite outgrowth and neurofilament expression in rat PC 12 cells elicited by a low dose of NGF that alone is insufficient to induce neuronal differentiation . ^^^ The potentiation of NGF activity by GM 1 appears to involve tyrosine autophosphorylation of Trk , which contains intrinsic tyrosine kinase activity that has been localized to the cytoplasmic domain . ^^^ In the presence of GM 1 in culture medium , there is a > 3 fold increase in NGF induced autophosphorylation of Trk as compared with NGF alone . ^^^ We also found that GM 1 could directly enhance NGF activated autophosphorylation of immunoprecipitated Trk in vitro . ^^^ Furthermore , such tight association of GM 1 with Trk appears to be specific , since a similar association was not observed with other growth factor receptors , such as low affinity NGF receptor ( p75NGR ) and epidermal growth factor receptor ( EGFR ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF stimulated retrograde transport of trkA in the mammalian nervous system . ^^^ The present study was designed to clarify the in vivo function of trkA as an NGF receptor in mammalian neurons . ^^^ The trkA retrograde transport and phosphorylation were enhanced by injecting an excess of NGF in the footpad and were abolished by blocking endogenous NGF with specific antibodies . ^^^ These results provide evidence that , upon NGF binding , trkA is internalized and retrogradely transported in a phosphorylated state , possibly together with the neurotrophin . ^^^ Furthermore , our results suggest that trkA is a primary retrograde NGF signal in mammalian neurons in vivo . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Mutational analysis of the nerve growth factor ( NGF ) receptor ( TrkA ) suggested that the binding of Shc to the activated receptor is required for NGF induced neuronal differentiation of PC 12 cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Numerous in vivo and in vitro studies have shown that NGF increases the expression of its receptors , p 75 and TrkA , in NGF responsive cell lines and in NGF responsive neurons of the developing and mature nervous system . ^^^ To determine if endogenous NGF is required for the normal developmental increase in p 75 and TrkA expression that occurs in sensory neurons shortly after they innervate their targets , we used quantitative RT / PCR to compare the levels of p 75 and trkA mRNAs in the trigeminal ganglia of normal mouse embryos and embryos that are homozygous for a null mutation in the NGF gene . ^^^ We show that the marked increase in p 75 and trkA mRNA expression that occurs between E 11 and E 13 in normal embryos takes place on time and to the same extent in NGF / embryos . ^^^ These findings clearly show that the expression of both p 75 and TrkA and the sensitivity of developing sensory neurons to NGF do not require and are not modulated by target derived NGF during the early stages of target field innervation . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) , brain derived neurotrophic factor , neurotrophin 3 ( NT 3 ) and NT 4 / 5 share similar protein structures and biological functions and interact with two different types of cell surface proteins , the Trk family of receptor tyrosine kinases , and the p 75 , or low affinity neurotrophin receptor . ^^^ Evidence indicates that co expression of the two genes for the p 75 receptor and the Trk NGF receptor can potentially lead to greater responsiveness to NGF , and suggests additional levels of regulation for the family of neurotrophin factors . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Recently , the second LRM of TrkA was identified as a functional nerve growth factor ( NGF ) binding site [ Windisch et al , J . ^^^ A peptide corresponding to this region effectively bound NGF and blocked binding of NGF to the recombinant extracellular domain of TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
A potential interaction of p 75 and trkA NGF receptors revealed by affinity crosslinking and immunoprecipitation . ^^^ Nerve growth factor binds independently to two transmembrane receptors , the p 75 neurotrophin receptor and the p140trk ( trkA ) tyrosine kinase receptor , which are both co expressed in the majority of neuronal cells that respond to NGF . ^^^ Here we have utilized affinity crosslinking agents with 125I NGF to detect an association of trkA and p 75 receptors in embryonic spinal cord and brain tissues enriched in the two receptors . ^^^ Although multimeric complexes of trkA and p 75 were not detected by affinity crosslinking , immunoprecipitation of cross linked NGF receptor complexes with trk specific antibodies resulted in selective immunoprecipitation of crosslinked p 75 . ^^^ Our results indicate that the trkA and p 75 receptors can potentially interact , and that such an association may be responsible for the generation of high affinity NGF binding sites . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immunohistochemistry , with TrkB and TrkA antisera , revealed that these neurons produced TrkB protein , the functional receptor for NT 4 / 5 and BDNF , but not TrkA protein , the high affinity receptor for NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Thus , astroglial cells in culture internalize NGF through a specific receptor mediated process , express trkA and full length trkB mRNAs at low levels , and respond to exogenous NGF by expressing a fibrous morphology under serum free culture conditions . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In contrast , trkA mRNA , which encodes the high affinity NGF receptor , was undetectable in either region . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Expression of p 75 in these variants occurs in the absence of expression of trkA , the gene encoding the high affinity nerve growth factor ( NGF ) tyrosine kinase receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The ovary also expresses some of the neurotrophin receptors , including p 75 NGFR , trkB [ the receptor for NT 4 / 5 and brain derived neurotropic factor ( BDNF ) ] , and trkA ( the NGF receptor ) . ^^^ The NGF and trkA genes showed a different pattern of expression , as the ovarian content of both NGF and trkA mRNA decreased at the time of folliculogenesis . ^^^ In contrast to the drop in NGF and trkA mRNA expression , NT 4 mRNA levels increased at the time of follicular assembly , coinciding with the abrupt appearance of trkB mRNA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In situ hybridization studies confirmed that the high affinity BDNF receptor ( TrkB ) was much more widely expressed in neurons than was the high affinity NGF receptor ( TrkA ) . ^^^ It is likely that binding of BDNF to TrkB , which appears to be more abundant and ubiquitous than TrkA , restricts the diffusion of BDNF relative to that of NGF . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To begin to analyze putative relationships of growth factor responsiveness and growth factor / growth factor receptor expressions , IMR 32 , GIMEN , and LAN 1 cell lines were studied for the presence of bFGF , NGF , FGF receptors ( R ) 1 ( flg ) and FGFR 4 , trk , and low affinity NGF receptor ( p 75 ) mRNAs . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Based upon these data we hypothesize that there is a defect in retrograde transport of NGF in AD which may be due to a abnormal production and / or utilization of the trk receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the rat aortic balloon deendothelialization model of vascular injury , the expression of NGF , BNDF , and their receptors trk A and trk B increased dramatically in the area of injury within 3 days and persisted during the formation of the neointima . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Deletion of a conserved juxtamembrane sequence in Trk abolishes NGF promoted neuritogenesis . ^^^ Deletion of a conserved juxtamembrane sequence ( KFG ) in the Trk NGF receptor resulted in impaired neurite outgrowth , somatic hypertrophy , and induction of c fos , c jun , and TIS 1 immediate early genes . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Experiments over the past decade in which NGF / TrkA signaling has been abolished by antibodies or targeted gene mutations have shown that 70 85 % of dorsal root ganglion ( DRG ) neurons require NGF for survival during development . ^^^ These neurons express the signaling receptor for NGF , TrkA . ^^^ There is a major discrepancy , however , between the percentage of DRG neurons which require NGF for survival ( 70 85 % ) and percentage of DRG neurons expressing TrkA receptors ( 40 50 % ) . ^^^ The identity of these non TrkA expressing , NGF dependent neurons has not been established . ^^^ However , in mutant mice in which NGF / TrkA signaling has been abolished by inactivation of the trkA gene , BSI staining in the DRG and dorsal horn is completely eliminated . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Human neuroblastoma cell lines frequently express the TRK A proto oncogene and bind nerve growth factor ( NGF ) but do not differentiate when exposed to NGF . ^^^ Transient transfection of an exogenous TRK A gene into SH SY5Y and LA N 5 neuroblastoma cells restored the ability of these tumor cells to differentiate with NGF . ^^^ Stable TRK A transfected SH SY5Y cell clones were isolated , and they responded to NGF by autophosphorylation of p140trk A , c fos induction , morphological differentiation , and increased expression of two neuronal marker genes , neuropeptide tyrosine and GAP 43 . ^^^ In phorbol ester induced differentiated wild type cells , TRK A expression was increased with no change in NGF responsiveness . ^^^ Thus , the restoration of the NGF induced differentiation pathway by exogenous TRK A presents a system of NGF responsive human cultured cells and focuses attention on the trk A protein and its function or malfunction in neuroblastoma . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
On the basis of the recent identification of a nerve growth factor ( NGF ) binding site within TrkA , the ability of the different structural entities within the extracellular domain of TrkB to bind the various neurotrophins was determined by using a recombinant receptor approach . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
However , in the presence of NGF , NT 3 was unable to induce sphingomyelin hydrolysis , raising the possibility that Trk was modulating p75NTR dependent sphingomyelin hydrolysis . ^^^ Inhibition of Trk tyrosine kinase activity with 200 nM K252a enabled both NGF and NT 3 in the presence of NGF to induce sphingomyelin hydrolysis . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have exploited a battery of approaches to address several controversies that have accompanied the expansion of the nerve growth factor ( NGF ) family of neurotrophic factors and the identification of the Trk tyrosine kinases as receptors for these factors . ^^^ We also find that all of the Trks display similar dose responses to their `` preferred ' ' ligands in neuronal as compared with nonneuronal cells ( i . e . , NGF for TrkA , BDNF and NT 4 / 5 for TrkB , and NT 3 for TrkC ) , providing evidence against a role for accessory molecules expressed in neurons in generating receptors that would allow for responses to lower concentrations of the neurotrophins . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the present study , immunoprecipitates of Trk NGF receptors from PC 12 cells ( + / NGF treatment ) were assayed for protein kinase activity by using the substrates myelin basic protein and histone HF 1 under phosphorylating conditions optimal for protein kinase N and in the presence or absence of purine analogs . ^^^ Analysis of myelin basic protein phosphorylated by anti Trk immunoprecipitates revealed an NGF stimulated increase in phosphothreonine and phosphotyrosine . ^^^ Neither 2 aminopurine nor 6 thioguanine inhibited the NGF dependent induction of Trk associated kinase activity . ^^^ Our findings thus indicate association of a purine analog sensitive serine / threonine protein kinase activity with Trk NGF receptors . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Phosphorylation experiments indeed showed that BDNF , NT 3 , and NT 4 produced rapid tyrosine phosphorylation of Trk proteins , as detected by immunoprecipitation using a pan Trk specific antibody , whereas NGF produced no detectable tyrosine phosphorylation in hippocampal cultures . ^^^ Cultures of embryonic day 18 ( E 18 ) hippocampal neurons were also found by Northern analysis to express trkB and trkC but not trkA , indicating potential responsiveness to brain derived neurotrophic factor ( BDNF ) , neurotrophin 3 ( NT 3 ) , and NT 4 , but not NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
However , Grb 2 does not bind to NGF activated Trk receptors . ^^^ Mitogenic signaling of NGF in NIH 3T3 cells ectopically expressing Trk receptors also takes place without detectable association between Grb 2 and Trk . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This has been proven by ( 1 ) direct effect of NGF on [ 3H ] thymidine incorporation , ( 2 ) inhibition of autocrine keratinocyte growth by monoclonal antibodies ( alpha D 11 ) inhibiting human NGF biological activity , and ( 3 ) inhibition of autocrine keratinocyte proliferation by a trk specific inhibitor , the natural alkaloid K252a . ^^^ The trkA protooncogene product ( p140trkA ) , a component of the NGF receptor , is not expressed by keratinocytes . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) induces both differentiation and survival of neurons by binding to the Trk receptor protein tyrosine kinase . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Because of the synergistic effects of DHT and NGF , the regulation of NGF receptor mRNA by DHT was evaluated ; however , no significant induction of either trkA or p 75 mRNA expression by androgen was documented . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In mutant PC 12 nnr 5 cells that lack the Trk NGF receptor , the purine analogue sensitive p 75 associated kinase activity was not inducible by NFG . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Finally , in PC 12 cells , NGF stimulated tyrosine phosphorylation of SNT was dependent on the levels of Trk tyrosine kinase activity and was constitutively induced by expression of pp60v src . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We document the presence of RNA message for the low ( LNGFR ) and the high affinity NGF receptor ( NTRK 1 ) by using RT PCR on fresh BM aspirate and on LTBMC . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Both the mitogenic activity of NGF , as well as the receptor linked tyrosine kinase activity , can be abrogated in BON cells by the trkA inhibitor K 252a and specific anti NGF antibody . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF induced phosphorylation of the trkA receptor , activated a cascade of cellular intermediaries such as phospholipase C gamma 1 and ERK proteins , and stimulated c fos gene transcription in all trkA expressing clones . ^^^ NGF mediated neuronal differentiation was observed solely in trkA expressing B 104 derived clones and was characterized by reduced cell growth , activation of NGF regulated genes , and downregulation of the endogenous low affinity NGF receptor gene ( gp75NGFR ) . ^^^ No such phenotypical changes occurred in trkA expressing C 6 or C 7 derived clones following NGF treatment . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Our findings of extensive colocalization of p 75 with trkA and trkB lend support to the idea that p 75 is important in mediating the actions of NGF and brain derived neurotrophic factor on DRG neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In contrast , expression of mRNAs encoding choline acetyltransferase , p 75 low affinity NGF receptor , neurotrophin tyrosine kinase receptors Trk and TrkB , and brain derived neurotrophic factor showed neuronal sparing in several other regions of the brain . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In this study , we analyzed the NGF level in wound fluid by a sensitive enzyme immunoassay and correlated the NGF level with the cytological localization of NGF , low affinity NGF receptor ( p75NGFR ) , and Trk receptor in the axotomized nerve by immunohistochemistry . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Using combined isotopic and non isotopic in situ hybridization , we found that neurons in developmental estrogen targets ( e . g . , the cerebral cortex ) , co localized mRNAs for the neurotrophins ( NGF or BDNF ) with their cognate receptors ( p75NGFR [ the pan neurotrophin receptor ] and trkA or trkB [ the tyrosine kinase receptors ] ) , suggesting a localization of neurotrophin autocrine loops to these estrogen sensitive neurons . ^^^ Reciprocally , estrogen up regulated trkA mRNA and transiently down regulated p75NGFR mRNA , suggesting that estrogen may increase the efficiency of NGF binding in PC 12 cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Like neuronal cells , insulin producing cells ( beta cells ) possess nerve growth factor ( NGF ) binding sites and express mRNA coding for the low and high affinity NGF receptors , p75NGFR and Trk A respectively . ^^^ By polymerase chain reaction , immunocytochemistry , cross linking and Western blot analysis , we clearly demonstrated that Trk A and p75NGFR , the two NGF receptors expressed in INS 1 cells and PC 12 cells are similar . ^^^ Moreover , upon NGF treatment , Trk A is phosphorylated on tyrosine residues in both cell types in the same dose and time dependent manner . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Results for trkA expression indicate an increase in expression at days 4 6 post op in both groups of animals , with the anti NGF treatment having a delayed influence on mRNA levels . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Changes in the expression of mRNA encoding NGF , the low and high affinity receptors for NGF ( p 75 and p 140 trk , respectively ) and choline acetyltransferase ( ChAT ) were also determined . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The high affinity receptor for NGF is the proto oncogene product , p140trkA ( trkA ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have demonstrated the expression of Trk A messenger RNA coding for the high affinity NGF receptor in islet cells and the localization of Trk protein in both alpha and beta islet cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Because GM 1 appears to enhance nerve growth factor ( NGF ) activity , we have used C6trk+ cells , a derivative of C 6 2B glioma cells that express the high affinity receptor for NGF trkA , to determine whether the neurotrophic effects of GM 1 occurs through induction of trkA activity . ^^^ Exposure of C6trk+ cells to NGF ( 10 50 ng / ml ) resulted in a five to 10 fold increase in trkA tyrosine phosphorylation within 5 min . ^^^ In addition , GM 1 potentiated the NGF mediated activation of tyrosine phosphorylation of trkA . ^^^ Thus , our data demonstrate that GM 1 mimics some of the effects of NGF and suggest that the neurotrophic properties of GM 1 may be attributed to its activation of trkA signal transduction . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Binding of neurotrophins to receptors encoded by the gene family trk initiates signal transduction into the cell . trkA interacts preferably with nerve growth factor ( NGF ) , trkB with brain derived neurotrophic factor ( BDNF ) and neurotrophin 4 / 5 ( NT 4 / 5 ) and trkC with neurotrophin 3 ( NT 3 ) . ^^^ Chimeras of trkC where this domain was exchanged for the homologous sequences from trkB or trkA gained high affinity binding to BDNF or NGF respectively , while deletion of this domain in trkC or trkA abolished binding to NT 3 or NGF respectively . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The time course of the effects is consistent with a direct up regulation of ChAT followed by either direct or indirect down regulation of p75NGFR and trkA NGF receptors , possibly due to increased cholinergic activity in the hippocampal formation and cortex and a decrease in hippocampal levels of NGF . ^^^ Current evidence suggests ChAT , p75NGFR , trkA , and NGF all play a role in regulating cholinergic function in the hippocampal formation and cortex . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In PC 12 cells expressing trkB ( Ip et al . , 1993 ) , the increase in Na current density caused by brain derived neurotrophic factor ( BDNF ) was similar to that observed upon activation of endogenous trkA by NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Upregulation of the trkA and low affinity NGF receptors ( LNGFR ) occurred after 3 days of NGF + aphidicolin treatment and required treatment with both NGF and aphidicolin . ^^^ In response to NGF in the absence of aphidicolin , the TrkA transformant line ceased proliferation and irreversibly differentiated . ^^^ Hence , expression of NGF receptors is upregulated during differentiation of SH SY5Y cells , and overexpression of TrkA enhances NGF induced differentiation . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
It has been proposed that the high affinity nerve growth factor ( NGF ) receptor required for NGF response is a complex of two receptor proteins , gp 75 and the tyrosine kinase TrkA , but direct biochemical or biophysical evidence has been lacking . ^^^ We found that gp 75 is relatively mobile on TrkA negative nnr 5 cells , a PC 12 variant which is nonresponsive to NGF . ^^^ Immobilization was found to require intact TrkA kinase and gp 75 cytoplasmic domains , paralleling the requirements of high affinity binding of NGF . ^^^ Analysis of gp 75 diffusion coefficients indicates that mutated gp 75 and TrkA molecules may form a complex , even in the absence of the ability to bind NGF with high affinity . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Since NGF neurotropic effects are transduced by the ' trk ' gene product 140 kDa tyrosine kinase receptor , gp140trk , we investigated the role of gp140trk and tyrosine phosphorylations in staurosporine neurotropic effects . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Our findings indicate that GM 1 promoted survival can be mediated in part by the Trk NGF receptor as well as by TrkB , and potentially by tyrosine kinase receptors for additional neurotrophic growth factors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In this report we have characterized the expression of the signal transducing component of the NGF receptor , the Trk tyrosine receptor kinase , in prostate epithelial cells that bind exogenous NGF beta and an endogenous NGF beta immunoreactive protein in hPS . ^^^ Stimulation of TSU pr 1 cells with either NGF beta or hPS induced tyrosine phosphorylation of Trk proteins , whereas no phosphorylation was evident in untreated cells , cells treated with hPS immunoprecipitated with anti NGF beta antibody , or brain derived neurotrophic factor and neurotrophin 3 treated cells . ^^^ These results demonstrate a functional Trk receptor in the epithelia of the human prostate that is responsive to exogenous NGF beta and an endogenous NGF beta immunoreactive protein in hPS , thereby supporting the concept of the paracrine regulation of growth in the human prostate via a stromal neurotrophin epithelial Trk receptor interaction . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
PNT 1 was shown to efficiently block the chemical crosslinking of NGF , BDNF , and NT 3 to their cognate Trk receptors and to the low affintiy NGF receptor expressed on neuronal and nonneuronal cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
It was previously demonstrated that the high affinity NGF receptor , Trk A , which is sufficient for NGF signal transduction , is expressed in different beta cell lines and in normal rat islet cells in primary culture . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Neurotrophins such as nerve growth factor ( NGF ) mediate their effects through interactions with high affinity tropomycin related kinase ( trk ) receptors . ^^^ Colocalization studies revealed that between 66 % and 76 % of trk immunoreactive basal forebrain neurons also expressed immunoreactivity for the low affinity p 75 NGF receptor , an excellent marker for cholinergic basal forebrain cells . ^^^ In this experiment , most single labeled basal forebrain neurons contained only trk immunoreactivity , whereas 4 % of basal forebrain neurons expressed only the low affinity p 75 NGF receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Because NGF , BDNF , NT 3 , and NT 4 / 5 bind to p 75 with similar affinity , p 75 may either act as a common subunit in a neurotrophin receptor complex with trk family members , or act by independent mechanisms to mediate biological actions of each neurotrophin . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Accumulating evidence indicates that the Trk family of tyrosine protein kinase receptors , Trk ( also known as TrkA ) , TrkB , and TrkC , are responsible for mediating the trophic effects of the NGF family of neurotrophins . ^^^ Nerve growth factor ( NGF ) specifically recognizes Trk , a receptor identified in all major NGF targets , including sympathetic , trigeminal , and dorsal root ganglia as well as in cholinergic neurons of the basal forebrain and the striatum . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The initial event in the neuronal differentiation of PC 12 cells is the binding of the neurotrophin nerve growth factor ( NGF ) to the Trk receptor . ^^^ To transmit NGF signals , NGF activated Trk rapidly associates with the cytoplasmic proteins , SHC , PI 3 kinase , and PLC gamma 1 . ^^^ This review will discuss the potential roles of Trk and the proteins of the Trk signalling pathways in NGF function , and summarize our attempts to understand the mechanisms used by Trk to generate the many phenotypic responses of PC 12 cells to NGF . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The nerve growth factor ( NGF ) family of neurotrophins exerts effects by binding to products of the trk family of proto oncogenes . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Cells that lack the high affinity receptor component ( trkA ) for nerve growth factor ( NGF ) are unresponsive to NGF . ^^^ We investigated whether C 6 2B cells , a rat glioma derived cell line , express trkA and , as a consequence , are responsive to NGF . ^^^ Cross linking of 125I labeled NGF to PC 12 cells identified two major bands with an apparent molecular weight of 158 kDa and 100 kDa corresponding to trkA and p75NGFR , respectively . ^^^ In C 6 2B cells stably transfected with the rat trkA cDNA , NGF increased c fos mRNA , induced tyrosine phosphorylation of gp140trk , and SNT ( suc associated neurotrophic factor induced tyrosine phosphorylated target ) , and caused morphological changes within 72 h . ^^^ All of these effects of NGF were blocked by the protein kinase inhibitor K 252a suggesting that NGF signal transduction was restored by trkA expression . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Maximal inhibition of VGF mRNA induction was achieved using K 252a , an inhibitor of the NGF receptor Trk tyrosine kinase , and by mutating both Y 490 ( SHC association site ) and Y 785 ( PLC gamma 1 association site ) of Trk . ^^^ The binding of NGF to Trk therefore activates redundant signal transduction pathways which converge to regulate vgf gene expression . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immunohistochemical localization of the high affinity NGF receptor ( gp 140 trkA ) in the adult human dorsal root and sympathetic ganglia and in the nerves and sensory corpuscles supplying digital skin . ^^^ Recently , a protein tyrosine kinase of congruent to 140 kDa molecular weight , encoded by the proto oncogene trkA , has been identified as the high affinity NGF receptor ( gp 140 trkA ) . ^^^ CONCLUSIONS : Present results provide evidence for the localization of gp 140 trkA like IR in : ( 1 ) nerve cells which are known to be NGF responsive , and ( 2 ) non nervous cutaneous tissues which are innervated by NGF dependent peripheral neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Tyrosine protein kinases TrkA and TrkC are signal transducing receptors for nerve growth factor ( NGF ) and neurotrophin 3 ( NT 3 ) , respectively . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These melanoma lines express low affinity neurotrophin receptor p75NTR in relation to their brain metastatic potentials but the variants do not express trkA , the gene encoding a high affinity nerve growth factor ( NGF ) tyrosine kinase receptor p140trkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The binding of NGF delta 9 / 13 to Sf 21 cells ectopically expressing the TrkA NGF receptor was also abolished . ^^^ Our results support the conclusion that the NH 2 terminal domain encompassing residues 1 9 and 9 13 is essential for maintaining the binding capability of NGF for high affinity TrkA receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The detection of relatively high amounts of NGF synthesis in the BF S was supported in studies demonstrating rapid NGF receptor ( Trk ) activation in the basal forebrain by exogenous NGF and in experiments showing that NGF mRNA was inducible in the BF S by 1 , 25 dihydroxyvitamin D 3 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Incubation of human B lymphocytes with 10 nM K252a , an inhibitor of Trk kinase , decreased NGF induced microfilament assembly by 75 % . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA expression in the CNS : evidence for the existence of several novel NGF responsive CNS neurons . ^^^ TrkA is a receptor for NGF . ^^^ To further define NGF actions in the CNS , we examined trkA expression in the adult rat brain . ^^^ In contrast to trkA , p75NGFR was found only in a minority of NGF responsive populations . ^^^ Our data provide further evidence that expression of trkA marks NGF responsive CNS neurons and suggests novel roles for NGF in the brain . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the present study , we used immunocytochemistry to show that the high affinity NGF receptor protein , gp140trk ( trk ) is detectable in embryonic spinal tissue sections and in cord dissociates . ^^^ Correlation of trk expression with NGF induced chemotaxis revealed that both the receptor protein expression and functional responses to NGF develop along a ventro dorsal gradient that parallels the in vivo pattern of neurogenesis and migration . ^^^ Analysis of the temporal changes in trk immunoreactivity demonstrated that expression of gp140trk is bimodal , possibly reflecting multiple effects of NGF during development . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Potent competitive antagonists were derived from the NGF beta turn C D , which inhibited [ 125I ] NGF binding to TrkA receptors and specifically inhibited optimal NGF mediated neurite outgrowth in PC 12 cells . ^^^ The cyclic beta turn A ' A ' ' analog also inhibited NGF binding to TrkA receptors but with lower potency . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have analyzed murine CD4+ T cell clones for their ability to express transcripts encoding NGF , low affinity NGF receptor , and trk protooncogene , the signal transducing receptor subunit for NGF . ^^^ G4 . 1 , express NGF and Trk mRNA after appropriate activation with mitogen or with antigen and antigen presenting cells . ^^^ NGF and trk induction occurred to a similar extent and over a similar time course in activated 8 / 37 T cells , raising the possibility that NGF and trk genes are under coordinate control . ^^^ Our finding that activated CD4+ T cell clones not only express Trk but also synthesize and release biologically active NGF implicates NGF as an autocrine and / or paracrine factor in the development and regulation of immune responses . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA , a tyrosine kinase receptor , is an essential component of the nerve growth factor ( NGF ) response pathway . ^^^ Both IgG and Fab fragments block binding of NGF to trkA expressed by the PC 12 cell line . ^^^ In NGF binding studies using anti trkA and anti low affinity NGF receptor ( LNGFR ) immunoglobulin ( Ig ) G , essentially all binding of NGF can be inhibited . ^^^ The results imply that > or = 97 % of the NGF binding sites on PC 12 cells are accounted for by trkA and the LNGFR . ^^^ The binding data also argue that all low affinity NGF binding sites on PC 12 cells reflect interactions with the LNGFR , while all high affinity sites are trkA dependent . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To extend this work , we have examined the effects of estrogen replacement on relative levels of choline acetyltransferase ( ChAT ) , trkA , and nerve growth factor ( NGF ) mRNAs within different regions of the basal forebrain and hippocampal formation using quantitative in situ hybridization techniques . ^^^ In contrast , estrogen replacement resulted in significant decreases in relative levels of NGF mRNA in the hippocampus and of trkA mRNA in the MS and nBM ( but not in the HDB or the striatum ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have examined a group of WT immunohistochemically with antibodies recognizing known trk receptor proteins , the p 75 receptor , and the NTs , NGF and NT 3 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To determine the role of neurotrophins on the initial development of the avian embryo , RT PCR was used to detect when mRNA for nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , and neurotrophin 3 ( NT 3 ) , as well as their respective receptors , trkA , trkB , and trkC , is first expressed in the avian embryo . trkA , BDNF , trkB , NT 3 , and trkC mRNA were expressed as early as stage 1 ( `` prestreak ' ' stage ) , while NGF mRNA was not expressed until later in development ( stage 5 , `` notochord ' ' stage ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The potency of binding of all hNGF variants to the low affinity NGF receptor p 75 was largely unaffected indicating distinct structural contributions of the NH 2 terminal region of hNGF to the binding to TrkA versus p75 . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Differentiated RN46A cells express low affinity nerve growth factor ( NGF ) receptor ( p75NGFR ) and are immunoreactive using an antibody that recognizes the carboxy terminal 13 amino acids of all three trk proteins ( pan trk ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These results show that glial cells present in a reactive gliosis which develops in the kainic acid lesioned thalamus , do not synthesize neurotrophins but instead produce high levels of both low and high affinity NGF receptors , LNGFR by Schwann cells / oligodendrocytes and possibly a subset of microglial cells , and trkA by reactive astrocytes . ( ABSTRACT TRUNCATED AT 400 WORDS ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
While Shc is also found bound to the activated NGF receptor , Trk , no complexes were detectable that contained both Trk and Grb 2 or Sos . ^^^ Higher concentrations of TRK Y490P inhibit tyrosine phosphorylation of Shc and the formation of Shc complexes with Grb 2 : this results in strong inhibition of Ras activation by NGF and partial inhibition of Ras activation by EGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We now report that melanocyte stimulation with phorbol 12 tetra decanoate 13 acetate ( TPA ) , previously reported to induce p 75 NGF receptor , also induces trk in melanocytes , and TPA effect is further potentiated by the presence of keratinocytes in culture . ^^^ Moreover , trk in melanocytes becomes phosphorylated within minutes after NGF stimulation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF binding to p75NGFR inhibited the toxicity of beta amyloid peptide , whereas NGF binding to TrkA , the high affinity NGFR , enhanced it . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The expression of high affinity neurotrophin receptors ( TrkA , TrkB , and TrkC ) determines the survival response of different populations of neurons to specific members of the neurotrophin family , including nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , and neurotrophin 3 ( NT 3 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA , a member of the receptor tyrosine kinase family , binds nerve growth factor ( NGF ) and subsequently activates intracellular signaling pathways . ^^^ Previous studies have found variable and weak interaction of the TrkA receptor with neurotrophin 3 ( NT 3 ) , another member of the NGF family . ^^^ Function perturbing antibodies to the p 75 low affinity NGF receptor potentiated the NT 3 responses of both forms of TrkA in the transfected PC12nnr5 cell lines , suggesting that the low affinity NGF receptor suppresses the ability of TrkA to respond to NT 3 . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Expression of mRNAs for trk protooncogene and NGF low affinity receptor gene ( LNGFR ) were analyzed in 45 neuroblastomas with Northern Blot . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Clinical response to retinoic acid was noted only in the two children with tumors coexpressing trk protooncogene mRNA , encoding an essential part of the nerve growth factor ( NGF ) high affinity receptor , and low affinity NGF receptor gene ( LNGFR ) mRNA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Three cell lines stably transfected with TRK A exhibited early responses to NGF stimulation , but neurite extension was not observed . ^^^ Our results indicate that endogenous TRK A in non responsive cell lines is either defective , or present in amounts below a threshold level required to elicit measurable responses to NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF induces terminal differentiation in trkA expressing neuroblastoma cells in vitro and in vivo . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Developmental changes in nerve growth factor ( NGF ) binding and NGF receptor proteins trkA and p 75 in the facial nerve . ^^^ This study characterizes the temporal spatial distribution of nerve growth factor ( NGF ) low ( p 75 ) and high affinity ( trkA ) receptors in the facial nerve and geniculate ganglion ( GG ) of developing quail embryos ( E 3 to E 14 ) . ^^^ In addition , expression of trkA and p 75 protein like immunoreactivity in the facial nerve and GG was studied by Western blot , in order to distinguish between high and low affinity NGF receptors respectively . ^^^ The temporal pattern of p 75 expression matches the pattern of quantitative binding of NGF , while the trkA expression is restricted to a few stages mainly E 7 and E 9 , implying that most of the binding detected is via low affinity receptors , except for a proportion of high affinity receptors present at stages of maximum binding . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have examined the mechanisms controlling the induction of the two NGF receptors , trkA and p 75 , in proliferating neuroblasts immuno isolated from thoracolumbar embryonic sympathetic ganglia . ^^^ Rather , this receptor is induced by environmental signals including NT 3 , which also acts as an interim survival factor for these neuroblasts . trkA induction by NT 3 is consequent to its promotion of mitotic arrest , as anti mitotic drugs also efficiently induce trkA . p 75 expression is induced in trkA expressing cells by NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Similarly , no difference in the expression of the mRNA for NGF or its high affinity receptor ( trkA ) , were observed at 6 h , 1 or 7 days following SCI . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The sensory deficit in mice with mutated p75NGFR suggests it is necessary for development of sensory neurons ; however , whether it is required , in addition to trkA , for signal transduction or is more involved in localization of NGF is unresolved . ^^^ Thus , p75NGFR undergoes a switch in function in the perinatal period : during embryogenesis it is required , probably with trkA , to mediate neuronal survival in the presence of NGF , but in the early postnatal period it acts as a constitutive death signal in the absence of NGF . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This effect can be prevented by the addition of both an anti NGF neutralizing antibody and a high affinity NGF R ( trk ) specific inhibitor , the natural alkaloid K252a . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Selective coexpression of insulin receptor related receptor ( IRR ) and TRK in NGF sensitive neurons . ^^^ Using in situ hybridization and immunohistochemistry , we now show that the expression of this receptor is selectively concentrated in a subset of neurons where its appearance is closely associated with that of the NGF receptor TRK . ^^^ These findings are consistent with a functional linkage of the IRR and TRK receptors in NGF sensitive neurons . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We first examined the basal forebrain tissues for developmental changes in expression of the high affinity NGF receptor ( trkA ) gene . ^^^ Then we determined the effect of NGF on trkA gene expression in serum free cultures of basal forebrain neurons from 17 day fetal rats . ^^^ NGF was found to induce trkA mRNA 36 h after the addition of NGF , while no trkA mRNA was detected in the absence of NGF . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Mice deficient for nerve growth factor ( NGF ) and its high affinity receptor , encoded by the trkA proto oncogene , suffer from complete loss of sympathetic neurons and sensory neurons responsive to temperature and pain . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Expression and functionality of the trkA proto oncogene product / NGF receptor in undifferentiated hematopoietic cells . ^^^ The expression of the low affinity NGF receptor ( p 75 ) and the trkA proto oncogene product was analyzed in a series of human hematopoietic cell lines at protein and RNA levels . ^^^ In addition , NGF induced autophosphorylation of TrkA and could substitute for granulocyte monocyte colony stimulating factor to trigger the proliferation of the TF 1 cell line , with a half maximal signal observed at 50 pmol / L , indicating that p 75 is not required for DNA synthesis in this cell line . ^^^ The physiologic relevance of NGF in early hematopoiesis was confirmed by showing that 12 % to 15 % of progenitor blood cells from mice treated with 5 fluorouracil expressed TrkA and that these cells could be induced to proliferate and differentiate in response to NGF in association with macrophage colony stimulating factor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In contrast , responsiveness to the TrkA ligand NGF was absent in the ebmryo and increased during the first 2 weeks after birth in various brain areas , particularly in striatum , basal forebrain , and hippocampus . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF , neurotrophin 3 ( NT 3 ) , and neurotrophin 4 ( NT 4 ) ) that bind and activate three different Trk receptors ( i . e . ^^^ Recently , amino acid residues in these variable loop regions have been implicated in the interaction between NGF and its signal transducing receptor TrkA . ^^^ Exchange of the 40 49 variable loop region between NGF and NT 3 resulted in molecules capable of activating both TrkA and TrkC receptors and of rescuing neurons containing TrkA and TrkC mRNAs , indicating that this loop plays an important role in determining biological specificities in these two neurotrophins . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The survival specificities of NGF and BDNF for different classes of chick neurons are maintained from the fish to the mammalian proteins , implying a conserved interaction with neuronal cell surface receptors ( of the Trk family ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The negligible effect of NGF seen in the bioassays agrees well with the expression of only a few trkA transcripts , encoding the high affinity receptor for NGF , in the CVG . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
High levels of BDNF transcripts were observed in the sensory epithelia of all vestibular end organs . mRNAs of low affinity NGF receptor , trkB and trkC , but not of trk , were expressed in the spiral and vestibular ganglia . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The glioma cell line C 6 was used to study the expression and growth dependent regulation of the nerve growth factor ( NGF ) tyrosine kinase receptor gp140trk , which is the mature protein product of the trk proto oncogene . ^^^ Immunocytochemical staining of C 6 cells with antibodies directed against either the low affinity NGF receptor gp75NGFR or trk proto oncogene products demonstrated a heterogeneous cellular distribution of both antigens . ^^^ Similar molecular weight species were found with anti Trk antibodies in the NGF treated cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Analysis of the trk NGF receptor tyrosine kinase using recombinant fusion proteins . ^^^ Comparative crosslinking indicates that NGF can recognize all trk receptor members , illustrating the large number of potential ligand receptor interactions between neurotrophins and their receptors . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This report show that the CD 4 positive T cell line 9 / 6 expresses trk protooncogene , the signal transducing receptor unit for NGF , after TCR mediated activation by Ag and APC . ^^^ Our findings that neither mitogen nor Ag stimulation induced the expression of the low affinity NGF receptor in 9 / 6 T cells indicate that trk alone is sufficient to mediate biologic activity of NGF in T lymphocytes . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The present studies were conducted to determine whether pharmacologically elevated levels of NGF are sufficient to cause subsequent stimulation of its high affinity receptor , as measured by increased levels of Trk phosphorylation . ^^^ Exogenously administered NGF ( 1 microgram , intracerebroventricularly ) led to a rapid ( 30 min ) and transient increase in Trk phosphorylation in the septum , which has high levels of NGF specific TrkA . ^^^ Dexamethasone mediated Trk phosphorylation was dose and time dependent , with peak increases being observed 12 hr after injection , concurrently with peak increases in NGF protein . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk / NGF receptor gene . ^^^ NGF interacts with the low affinity p 75 receptor and with Trk , a receptor tyrosine kinase encoded by the trk proto oncogene . ^^^ These findings demonstrate that Trk is the primary mediator of the trophic actions of NGF in vivo and that this signalling pathway plays a crucial role in the development of both the peripheral and the central nervous systems . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Trk receptors use redundant signal transduction pathways involving SHC and PLC gamma 1 to mediate NGF responses . ^^^ In response to NGF , the Trk receptor tyrosine kinase forms a complex with SHC , a protein that couples receptor tyrosine kinases to p21ras . ^^^ To determine the role of SHC and other Trk substrates in NGF signaling , Trk receptors with mutations in Y 490 and Y 785 ( the PLC gamma 1 association site ) were introduced into PC12nnr5 cells . ^^^ NGF treatment of PC12nnr5 cells expressing Trk with mutations in either substrate binding site resulted in normal neurite outgrowth and Erk 1 activity and tyrosine phosphorylation . ^^^ However , PC12nnr5 cells expressing Trk with mutations at both sites failed to stably extend neurites and efficiently induce Erk 1 activity and tyrosine phosphorylation in response to NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the central and peripheral nervous system and the phaeochromocytoma cell model PC 12 , NGF exerts its effects through the activation of the signalling capacity of Trk , a receptor tyrosine kinase ( RTK ) which upon interaction with NGF becomes phosphorylated on tyrosines and thereby acquires the potential to interact with signal transducing proteins such as phospholipase C gamma ( PLC gamma ) , phosphatidylinositol 3 ' kinase ( PI3 ' K ) and SHC . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Viral transduction of trkA into cultured nodose and spinal motor neurons conveys NGF responsiveness . ^^^ The trkA gene encodes the tyrosine kinase receptor that transduces the NGF signal . ^^^ We have used a defective herpes simplex virus 1 ( HSV 1 ) vector containing a full length rat trkA sequence ( pHSVtrkA ) to express NGF receptors in primary cultures of neonatal nodose neurons and embryonic spinal motor neurons which are normally unresponsive to NGF . ^^^ These observations indicate that nodose and spinal motor neurons can express the downstream signal transduction apparatus necessary to mediate the survival and differentiating effects mediated by ligand binding to trkA and that transduction with pHSVtrkA can effectively convert NGF nonresponsive neurons into responsive ones . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Many of these interactions are mediated by the neurotrophins NGF , BDNF , and NT 3 and the receptor tyrosine kinases encoded by genes of the trk family . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Trk , trkB , and trkC growth factor receptor genes were expressed in discrete subpopulations of sensory neurons but addition of NGF or brain derived neurotrophic factor ( BDNF ) did not inhibit the expression of c jun . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We examined the expression of genes encoding NGF , neurotrophin 3 ( NT 3 ) , and their putative high affinity receptors , trk A and trk C , respectively . ^^^ Trk A was detected in the trigeminal ganglion , while NGF was expressed in the central myelencephalon target , paralleling observations in the DRG and spinal cord . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Through transfection , trkA expression conferred NGF signaling leading to enhanced neuronal differentiation , including dose dependent induction of neurite outgrowth and a rapid transient increase in c fos and NGFI A mRNA . ^^^ These findings suggest that trkA transfection of neurons and neuronal precursors can be used to better define NGF signaling . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have transfected MAH cells , an immortalized sympathoadrenal progenitor cell line , with a plasmid encoding the 140 kDa Trk protein , a nerve growth factor ( NGF ) receptor with protein tyrosine kinase activity . ^^^ NGF promotes neurite outgrowth and proliferation from such cells , indicating that Trk is sufficient to mediate such responses in the absence of significant levels of the endogenous 75 kDa low affinity NGF receptor ( p 75 ) . ^^^ However , NGF is sufficient to promote terminal differentiation of a approximately 8 % of trk transfected MAH cells to postmitotic , NGF dependent neurons , whereas all cells eventually die in medium with bFGF . ^^^ Other environmental signals ( such as depolarization or ciliary neurotrophic factor ) can cooperate with NGF to enhance production of postmitotic NGF dependent neurons in trk transfected MAH cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
If this is the case , neurons in the prevertebral ganglia should express another neurotrophin receptor , in addition to the NGF receptor ( trkA ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have shown that the SH 2 domain of the adaptor protein Shc coimmunoprecipitates with all the Ret and Trk oncoproteins as well as with NGF activated proto Trk receptor . ^^^ Finally , when proto Trk product is stimulated by NGF , Shc phosphorylation and association with Grb 2 are induced . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have used a quantitative reverse transcription / polymerase chain reaction amplification technique to study the regulation of p 75 mRNA and trkA mRNA expression in developing NGF dependent trigeminal neurons . ^^^ Before becoming NGF dependent , these neurons express low levels of p 75 and trkA mRNAs in vivo . ^^^ With the acquisition of NGF dependence , p 75 and trkA mRNA levels increase markedly in vivo . ^^^ The level of trkA mRNA is sustained in neurons grown with NGF but is not up regulated by concentrations of NGF above those required to support survival . ^^^ These findings suggest that the expression of p 75 and trkA mRNAs are differentially regulated by BDNF and NGF at successive early stages of neuronal development . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Since no NGF mRNA nor the NGF high affinity receptor component trkA mRNA were detectable during the development of cochlear structures , this factor is not likely to be an important neurotrophin at this level . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have previously demonstrated that beta cells express both p75NGF R and Trk A , the low and high affinity nerve growth factor ( NGF ) receptors , respectively . ^^^ The increase in the concentration of the high affinity NGF binding sites is paralleled by an increase in Trk A protein without any change at the mRNA steady state level , suggesting a translational / posttranslational effect . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In situ hybridization techniques were used to examine the distribution and the nerve growth factor ( NGF ) regulation of trkA mRNA in the adult rat brain in order to identify neurons in discrete regions of the brain that may be NGF responsive . ^^^ Intracerebroventricular infusions of NGF into the third ventricle adjacent to the preoptic area resulted in a 58 % increase in relative cellular levels of trkA mRNA in the horizontal limb of the DBB . ^^^ These data provide evidence that both p75NGFR and trkA are expressed by NGF responsive neurons in the MS and DBB . ^^^ In addition , we note that areas that contained trkA mRNA and that also have been reported to contain p75NGFR are areas where high affinity NGF binding sites have been observed autoradiographically , whereas areas that contain either trkA or p75NGFR alone are areas where no high affinity NGF binding has been reported . ^^^ Together , these findings suggest that both trkA and p75NGFR play an important role in the formation of high affinity NGF receptors in brain and , furthermore , suggest that NGF may have physiological effects within many regions of the brain outside of the basal forebrain . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
On the other hand , expression of the high affinity NGF receptor ( trkA ) is restricted to cholinergic neurons in basal forebrain and striatum . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Ectopic trkA expression mediates a NGF survival response in NGF independent sensory neurons but not in parasympathetic neurons . ^^^ We have investigated the role of trkA , the tyrosine kinase NGF receptor , in mediating the survival response of embryonic neurons to NGF . ^^^ Embryonic trigeminal mesencephalic ( TMN ) neurons , which normally survive in the presence of brain derived neurotrophic factor ( BDNF ) but not NGF , become NGF responsive when microinjected with an expression vector containing trkA cDNA . ^^^ In contrast , microinjection of ciliary neurotrophic factor ( CNTF ) dependent embryonic ciliary neurons with the same construct does not result in the acquisition of NGF responsiveness by these neurons despite de novo expression of trkA mRNA and protein . ^^^ The failure of trkA to result in an NGF promoted survival response in ciliary neurons is not due to absence of the low affinity NGF receptor , p 75 , in these neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the present study , in situ hybridization was used to examine the expression of nerve growth factor ( NGF ) receptor ( p75NGFR ) , trk ( p140trk ) and trkB ( p145trkB ) mRNA in spinal cord sections from patients with amyotrophic lateral sclerosis ( ALS ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The biological responsiveness of neural cells to nerve growth factor ( NGF ) appears to require expression and ligand binding to both the low affinity NGF receptor ( LNGFR ) and the proto oncogene product trk , the latter being a receptor tyrosine kinase . ^^^ Immunolocalization of the LNGFR and the high affinity component of the NGF receptor , trk ( HNGFR ) was studied by electron microscopic morphometric analysis on cultured PC 12 pheochromocytoma cells , C 6 glioma cells and neonatal rat dorsal root ganglia neurons using a double immunogold labeling technique . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In addition , PC 12 cells expressing Wnt 1 ( PC12 / Wnt 1 ) fail to extend neurites after treatment with NGF , despite the presence and activation of high affinity NGF receptors encoded by the trk gene and the induction of early response genes . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Transfectants expressing the trkA mRNA and surface bound receptors transcriptionally activate immediate early genes ( c fos , c jun , and jun B ) following nerve growth factor ( NGF ) stimulation . ^^^ Genes selectively expressed in mature neurons ( SCG 10 , ret proto oncogene , GAP 43 , etc . ) are transcriptionally activated , and neurite outgrowth further demonstrates differentiation of transfectants following NGF stimulation . trkA expressing NB cells remain tumorigenic in nude mice ; however , subcutaneous treatment of tumor bearing mice with NGF induces Schwannian and neuronal cell differentiation similar to the induction seen in human ganglioneuroblastomas . ^^^ Thus , trkA expression in HTLA 230 cells is sufficient to generate a functional NGF receptor complex that leads to growth arrested and differentiated NB cells in vitro and in vivo in the presence of NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The mRNAs encoding the cognate neurotrophin receptors , p75NGFR , trkA , and trkB were expressed in the DRG throughout the post injury time course , suggesting that DRG neurons remain responsive to both NGF and BDNF . p75NGFR mRNA levels became transiently depressed in the DRG during the first several days after the lesion but returned to normal within 1 week . trkB mRNA was expressed in the normal sciatic nerve and levels were not altered by nerve crush . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We used polymerase chain reaction analysis to demonstrate the presence of NGF and trk mRNA in E 13 and E 14 cord cells , indicating the cells express message for both NGF and high affinity NGF receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor derived from terminals selectively increases the ratio of p 75 to trkA NGF receptors on mature sympathetic neurons . ^^^ In situ hybridization and image analysis were then used to determine neuronal levels of p 75 NGF receptor , trkA , and T alpha 1 alpha tubulin mRNAs , with the latter providing a correlative measure of neuronal sprouting . ^^^ These data therefore suggest that , in addition to promoting local sprouting , increased target derived NGF increases the levels of p 75 NGF receptor relative to trkA on terminal neurites , by differentially regulating receptor synthesis . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Since previous studies have shown that these three neurotrophins bind to the low affinity NGF receptor , p75NGFR , with similar affinity , our data suggest that the retrograde transport of neurotrophins by motoneurons may be mediated by additional components , such as the trk family of proto oncogenes . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In contrast , although the mRNAs for the NGF receptors p75NGFR and trkA were also expressed in DRG neurons from OVX and intact animals , expression of both NGF receptor mRNAs was upregulated in sensory neurons during proestrus , as compared to the OVX condition . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Mediation of NGF stimulated extracellular matrix invasion by the human melanoma low affinity p 75 neurotrophin receptor : melanoma p 75 functions independently of trkA . ^^^ Thus , these melanoma cells would not be expected to form functional p 75 p140 heterodimers or p 140 p140 homodimers capable of transducing an NGF generated signal to p140proto trkA cytoplasmic substrates . ^^^ In the absence of p140proto trkA , the matrix dependent effects of NGF on metalloproteinase expression of brain metastatic 70W melanoma cells suggest a signaling role for the low affinity melanoma p75NTR receptor and its associated purine analogue sensitive kinase in signaling enhanced matrix penetration of NGF rich stromal microenvironments such as the brain . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The low affinity p 75 neurotrophin receptor is believed to participate with the Trk receptor tyrosine kinase in the formation of high affinity binding sites for nerve growth factor ( NGF ) . ^^^ To investigate the functional significance of the two NGF receptors , a truncated p 75 receptor was stably expressed in PC 12 rat pheochromocytoma cells , yielding cells with greatly reduced levels of wild type p 75 and normal Trk levels . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA NGF receptor expression by non cholinergic thalamic neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA mRNA was undetectable , however , TrkB was present and upregulated by NGF in astrocytes but not oligodendrocytes . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
When p 75 was introduced by viral infection into fibroblast cells expressing the trk proto oncogene , a new binding site was created , consistent with high affinity NGF binding . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Trk immunoreactivity was observed in basal forebrain and striatal cholinergic neurons , whereas low affinity NGF receptor immunoreactivity was observed in basal forebrain but not striatal cholinergic neurons . ^^^ Since NGF exerts trophic actions on both basal forebrain and striatal cholinergic populations , the presence of Trk in these neurons lends strong support for an essential role of Trk in NGF responsive neurons , but suggests that the low affinity receptor is not necessary for NGF actions in the striatum . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Transfection with trk restores `` slow ' ' NGF binding , efficient NGF uptake , and multiple NGF responses to NGF nonresponsive PC 12 cell mutants . ^^^ Introduction of trk rescued all of the many and varied NGF responses assessed , including enhanced protein tyrosine phosphorylation , induction of immediate early and neural specific genes , neurite outgrowth and regeneration , maintenance of survival in serum free medium , and stimulation of AChE activity . ^^^ In contrast to PC12nnr5 cells , the trk transfected lines also bind and internalize NGF with wild type PC 12 cell characteristics . ^^^ Additionally , as no signaling defect other than the absence of trk expression was revealed in PC12nnr5 cells , this work supports the utility of this line for genetic dissection of the NGF mechanism of action . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In contrast to TrkA , the high affinity NGF receptor that transduces NGF signals for survival and differentiation , the function of the low affinity NGF receptor , p75NGFR , remains uncertain . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) and brain derived neurotrophic factor ( BDNF ) are neuronal survival molecules which utilize the Trk family of tyrosine kinase receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Neurotrophins homologous to the nerve growth factor ( NGF ) bind the neurotrophic receptors of the trk gene family . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NT 3 , NT 4 , and more prominently BDNF , induce neurite outgrowth from explant cultures of the E 10 trigeminal ganglia but no neurites are induced by NGF , despite the expression of trkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Tyrosine protein kinases trk , trkB and trkC are essential components of the high affinity receptors necessary to mediate biological effects of the neurotrophins NGF , BDNF , NT 3 and NT 4 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
CTB treatment ( 1 micrograms / ml ) enhanced NGF induced neurite outgrowth from PC 12 cells , NGF induced activation of ribosomal protein S 6 kinase , and NGF induced stimulation of trk phosphorylation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The neuron like differentiation of PC 12 cells is induced by nerve growth factor ( NGF ) through stimulation of a membrane bound protooncoprotein signaling pathway containing the NGF receptor Trk , the tyrosine kinase Src , and the GTP binding protein Ras . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Steady state mRNA levels for NGF , BDNF , and NT 3 , and their receptors , LNGFR , trk , trkB , and trkC , were examined in cultured rat Schwann cells . ^^^ NGF , BDNF , and LNGFR mRNAs were expressed in control Schwann cells , but NT 3 , trk , trkB and trkC mRNAs were not . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This report shows that human monocytes express the trk protooncogene , encoding the signal transducing receptor unit for NGF . ^^^ Treatment of monocytes with Staphylococcus aureus Cowan 1 , a potent activator of monocytes , stimulated trk mRNA synthesis in a time dependent way , implying a modulatory role for NGF in immune functions . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The members of this gene family , trk , trkB and trkC , bind a distinct neurotrophin of the nerve growth factor ( NGF ) gene family , and trigger the intracellular signals which elicit trophic and differentiating effects on neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The TRK T 1 oncogene , isolated from a human thyroid carcinoma , represents a rearranged form of the high affinity nerve growth factor ( NGF ) receptor encoded by the NTRK 1 gene ; it is created by an intrachromosomal rearrangement fusing the NTRK 1 tyrosine kinase domain to the 5 ' portion of the TPR gene . ^^^ We have investigated the effect of the TRK T 1 oncogene in PC 12 cells , a model system for studying neuronal differentiation and the mechanism of action of NGF . ^^^ Here , we report that , in PC 12 cells , the TRK T 1 oncogene has a differentiating effect that resembles that of NGF and requires the phosphorylation of the oncoprotein . ^^^ Our results are consistent with the hypothesis that TRK T 1 , as well as the original TRK oncogene , induces PC 12 differentiation by mimicking the action of NGF bound to its receptor . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The enhancement of chemotactic response and heparanase production was detected at NGF concentrations sufficient to fully saturate both low and high affinity NGF receptors ( NGFR ) , the neurotrophin receptor ( p 75 ) and the trkA gene product , respectively . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
K252a , a specific inhibitor of NGF induced trk p 140 autophosphorylation , did not alter the neuroprotection provided by EGF or bFGF , yet it completely abolished the protection provided by NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Expression of mRNA for the trk protooncogene , encoding a tyrosine kinase receptor essential for functional NGF signal transduction , and mRNA for the low affinity NGF receptor ( LNGFR ) was examined in 45 neuroblastomas and 3 benign ganglioneuromas using Northern blot analysis . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Members of the Trk tyrosine kinase family have recently been identified as functional receptors of the NGF family of neurotrophins . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
An extended surface of binding to Trk tyrosine kinase receptors in NGF and BDNF allows the engineering of a multifunctional pan neurotrophin . ^^^ Our results allowed us to combine structural elements from NGF , BDNF and neurotrophin 3 to engineer a pan neurotrophin that efficiently activates all Trk receptors and displays multiple neurotrophic specificities . . ^^^ Here we show that in nerve growth factor ( NGF ) and brain derived neurotrophic factor ( BDNF ) , discontinuous stretches of amino acid residues group together on one side of the neurotrophin dimer forming a continuous surface responsible for binding to and activation of TrkA and TrkB receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Forty three fresh tumor specimens of human neuroblastoma belonging to different clinical stages were analyzed for the expression of 2 proto oncogenes : trk , which encodes a tyrosine kinase receptor for nerve growth factor ( NGF ) and ret , another receptor type tyrosine kinase whose ligand is unknown . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Here we demonstrate that RINm5F , a rat insulinoma cell line representing an early stage in pancreatic beta cell differentiation , expresses both the Trk and p 75 NGF receptors and responds to NGF by extending neurite like ( neurofilament containing ) processes . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The retinoid produced a two to threefold increase in level of p75LNGFR mRNA ( the low affinity NGF receptor ) , without altering expression of the trk protoon cogene ( the high affinity NGF receptor carrying tyrosine kinase activity ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Il 1 beta also stimulates PGE 2 release , and this effect was inhibited by both NGF antibodies and a trk receptor blocker , NGF antibodies administered in vivo attenuated the increase in ovarian PGE 2 synthesis that antedates ovulation . ^^^ Immunoneutralization of NGF action or pharmacological blockade of trk tyrosine kinase activity targeted to one ovary resulted in the ipsilateral inhibition of ovulation . ^^^ We now report that trkA , the NGF receptor tyrosine kinase , is involved in the acute activational process that leads to the first ovulation . ^^^ NGF mRNA abundance also increases at proestrus , with peak values detected about 5 h before ovulation ; as in the case of trkA mRNA , NGF mRNA was found in thecal interstitial cells . ^^^ Both trkA and NGF protein , detected by immunohistochemistry , were localized to this same ovarian compartment . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Treatment of NIH 3T3 cells expressing human TrkA with nerve growth factor ( NGF ) resulted in a rapid cessation of growth . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This discovery suggests that the signaling NGF receptor , TrkA , can be used as a marker for nociceptive neurons . ^^^ In this study , we have used antibodies to TrkA , in conjunction with cell biological markers that show a restricted distribution in the DRG , to further characterize subsets of DRG neurons that are dependent upon NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Binding of nerve growth factor ( NGF ) to the TrkA receptor results in homodimerization , and activation of the intrinsic tyrosine kinase activity of the receptor , leading to multiple phosphorylations . ^^^ We investigated the in vivo formation and composition of the receptor complex induced by NGF in a central nervous system derived cell line ( B 104 neo ) , transfected with the human cDNA for TrkA . ^^^ Using receptor activated immunoprecipitation followed by analysis of the immune complexes by SDS PAGE and immunoblotting , we show that NGF induces the association of TrkA with c Crk 2 in a multimeric complex that also includes SHC and PLC gamma 1 . ^^^ While the tyrosine phosphorylation of TrkA , SHC and PLC gamma 1 increased with time in the presence of NGF and was inhibited by the tyrosine kinase inhibitor K252a , the state of tyrosine phosphorylation of c Crk 2 did not appear to change with NGF treatment . ^^^ These results clearly implicate c Crk 2 in the NGF signaling pathway and support the concept that more than one signaling molecule known to participate in the activation of Ras associates with TrkA upon NGF treatment . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Plasmalopsychosine was not capable of competing with cold chase stable , high affinity binding of NGF to Trk A , indicating that plasmalopsychosine and NGF differ in terms of Trk A activating mechanism . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This response was apparent by 24 h , did not occur with NGF treatment or when vector or TrkA NGFR were expressed and was reversed by dexamethasone pretreatment . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Our cellular data support the concept that staurosporine acts to inhibit the NGF receptor Trk ( Nye et al . : Mol Biol Cell 3 : 677 686 , 1992 ) , but that downstream steps can be activated by the higher concentration of staurosporine to bypass Trk and lead to neurite generation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA mediates an NGF survival response in NGF independent sensory neurons but not in parasympathetic neurons . ^^^ We have investigated the role of trkA , the tyrosine kinase NGF receptor in mediating the survival response of embryonic chicken neurons to NGF . ^^^ Embryonic trigeminal mesencephalic ( TMN ) neurons , which normally survive in the presence of BDNF but not NGF , become NGF responsive when microinjected with an expression vector containing rat trkA cDNA . ^^^ NGF promoted survival of embryonic neurons , but indicate that not all neurons are able to respond to a trkA mediated signal transduction event . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) has been shown to protect specific neurons that express its signaling receptor , trkA , from a variety of insults . ^^^ There are some data , in particular in the developing brain , indicating that NGF has neuroprotective actions that extend beyond cells expressing trkA . ^^^ NGF injection studies revealed that NGF stimulated tyrosine phosphorylation of trkA in multiple brain regions . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The presence of the neurotrophin , nerve growth factor , brain derived neurotrophic factor , neurotrophin 3 and neurotrophin 4 ( NGF , BDNF , NT 3 and NT 4 ) and their receptors of the tyrosine kinase family ( trkA , trkB and trkC ) have been investigated in the choroid plexus and dura mater of the adult rat by ribonuclease protection assay . ^^^ The choroid plexus contained high levels of mRNAs for NGF and NT 4 , and low levels of NT 3 and BDNF mRNA ; and high levels of trkB mRNA , and undetectable levels of trkA and trkC mRNA . ^^^ In the dura mater there were high levels of NT 3 and NGF , and low levels of BDNF and NT 4 mRNAs ; and high levels of trkC mRNA , and relatively high amount of trkB mRNA , while levels of trkA mRNA was undetectable . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Support for the latter hypothesis comes from our recent observations of co expression of estrogen receptor mRNA with the mRNAs for the neurotrophins and their receptors ; differential and reciprocal up regulation of estrogen and NGF receptor mRNA and protein expression by estrogen in adult female rat sensory neurons , PC 12 cells ; and cerebral cortical cultures ; and putative estrogen response elements in the NGF , BDNF , trkA and p 75 genes . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The high affinity NGF receptor is thought to be a complex of two receptors , gp 75 and the tyrosine kinase TrkA , but direct biochemical evidence for such an association had been lacking . ^^^ TrkA and gp 75 copatch in both the absence and presence of NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , and neurotrophin 3 ( NT 3 ) selectively bind to distinct members of the Trk family of tyrosine kinase receptors , but all three bind with similar affinities to the neurotrophin receptor p 75 ( p75NTR ) . ^^^ In the absence of TrkA , NGF binding to p75NGR activated the transcription factor nuclear factor kappa B ( NF kappa B ) in rat Schwann cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We show that in PC 12 cells expressing both TrkC and TrkA / nerve growth factor ( NGF ) receptors , different morphological changes occur upon addition of NGF or NT 3 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We performed high sensitivity flow cytometry and Western blotting to study the expression of the low affinity NGF receptor ( p75NGFR ) and of the transmembrane tyrosine kinase ( Trk ) family of high affinity receptors for the different neurotrophic factors on Epstein Barr virus ( EBV ) transformed human B lymphocytes . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We studied the effects of status epilepticus ( SE ) induced by lithium chloride / pilocarpine treatment on gene expression of neurotrophins of the nerve growth factor ( NGF ) family and of their high affinity receptors of the tyrosine protein kinase ( trk ) family in the forebrain . ^^^ NGF mRNA , but not the mRNA of its receptor trkA , was increased in the dentate gyrus . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Intraparenchymal NGF injections in adult and aged rats induce long lasting Trk tyrosine phosphorylation . ^^^ We therefore tested for effects of acute and chronic NGF treatment in vivo on the tyrosine phosphorylation response of Trk type neurotrophin receptors in adult and aged rats . ^^^ With 1 microgram of NGF injected , Trk type receptors were maximally stimulated from immediately after the injection until 3 days after the treatment . ^^^ Incubation of microslices of brain tissue from NGF injected animals in glucose free buffer completely abolished all Trk tyrosine phosphorylation signals . ^^^ Experiments with aged rats indicated similar extent and duration of Trk receptor activation after NGF administration in young adult and in aged brain . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA cleavage is regulated by protein kinase C and several receptor agonists ( including the TrkA ligand NGF ) , occurs at the ectodomain in a membrane proximal region , and is independent of lysosomal function . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We found that early hypothyroidism disrupted the developmental pattern of expression of the four neurotrophins , leading to relatively higher levels of NGF and neurotrophin 4 / 5 mRNAs and to a severe deficit in NT 3 and brain derived neurotrophic factor ( BDNF ) mRNA expression , without alteration in the levels of the full length tyrosine kinase ( trk ) B and trkC receptor mRNAs . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We found that intraparenchymal NGF elicits prolonged tyrosine phosphorylation of Trk type NGF receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In agreement with this result , the mRNA encoding the low affinity NGF receptor ( LNGFR ) was detected in ROS 17 / 2 . 8 cells , unlike trkA transcripts which encode the high affinity receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We exchanged the ligand binding domain of these receptors by the ectodomain of trkA and could thus control signaling by the new ligand , NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Both 5 and 50 ng of NGF / day failed to induce an effect on transmembrane protein tyrosine kinase trkA mRNA levels , but injections of 750 or 1500 ng / day of NGF up regulated trkA mRNA expression to approximately 2 fold of control . ^^^ NGF delivered intracerebroventricularly failed to induce an observable change in striatal trkA mRNA , even at a dosage of 4 . 5 micrograms of NGF / day . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Furthermore , colocalization studies show that many BDNF expressing sensory neurons also express trk A , the high affinity NGF receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Prevention by nerve growth factor ( NGF ) of apoptotic death in neural cells has been variously ascribed to binding of NGF to its low affinity ( p 75 ) or high affinity ( trkA ) receptor or to a cooperative interaction between the two . ^^^ In a series of studies using , in turn , neuroblastoma cell lines that express only p 75 , mutant NGF species that bind selectively to either p 75 or trkA , and a polyclonal antibody that binds to the NGF binding domain of p 75 , we demonstrate that NGF binding to p 75 is both necessary and sufficient for the abrogation of apoptosis in neuroblastoma cells treated with antimitotic agents . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Mutations in the TRKA / NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis . ^^^ Mice lacking the gene for TrkA , a receptor tyrosine kinase for NGF , share dramatic phenotypic features of CIPA , including loss of responses to painful stimuli , although anhidrosis is not apparent in these animals . ^^^ Our findings strongly suggest that defects in TRKA cause CIPA and that the NGF TRKA system has a crucial role in the development and function of the nociceptive reception as well as establishment of thermoregulation via sweating in humans . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
HTLA 230 , an NB cell line isolated from a patient with advanced disease , and its NGF receptor ( trkA ) expressing derivative ( 18 10 ) cells , consistently disseminated to the liver , the adrenal gland , and the bone marrow , but not the lungs . ^^^ Cell lines reestablished from 18 10 derived liver and bone marrow metastases maintained their cellular morphology , growth behavior , N myc overexpression , trkA expression , and functionally responded to NGF treatment , leading to growth arrest and neurite outgrowth . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The neurotrophins initiate signal transduction in responsive cells by ligand induced dimerization and activation of one of the Trk family of receptor tyrosine kinases ; NGF being specific for TrkA , BDNF and NT 4 / 5 for TrkB , and TrkC the preferred receptor for NT 3 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The high affinity NGF receptor , trkA , is selectively expressed by nociceptive sensory neurons particularly those containing sensory neuropeptides such as substance P and CGRP . 4 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The hyperalgesic actions of NGF may in part be the consequence of an increase in sensitivity of the peripheral terminals of high threshold nociceptors either as a result of a direct action of NGF on trkA expressing sensory fibres or indirectly via the release of sensitizing mediators from trkA expressing inflammatory cells and postganglionic sympathetic neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In rodent models of diabetes there are expression deficits in nerve growth factor ( NGF ) and in its high affinity receptor , trkA , leading to decreased retrograde axonal transport of NGF and decreased support of NGF dependent sensory neurons , with reduced expression of their neuropeptides , substance P and calcitonin gene related peptide ( CGRP ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) is considered to play a role in neurite outgrowth of small nerve fibres which express its high affinity receptor , trkA . ^^^ This study was designed to measure expression of messenger RNA ( mRNA ) coding for NGF and its receptors , trkA and p75NGFR , during nerve regeneration and degeneration in rats with streptozotocin induced diabetes ; mRNA coding for preprotachykinin A ( the substance P precursor ) , whose expression is stimulated by NGF , and mRNA for growth associated protein 43 ( GAP 43 ) were also measured in blots from L 4 + L 5 ( pooled unilaterally ) dorsal root ganglia . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These findings suggest that p 75 , in addition to trkA , also may be important in mediating the action of NGF on the synthesis of SP in the DRG following peripheral inflammation . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The effect of NGF on PC 12 migration was blocked by K 252a , a selective inhibitor of the trk family of receptor tyrosine kinases . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) , the ligand to the tyrosine kinase receptor Trk A , was also included . aFGF and GH were found to stimulate insulin release to the culture medium , whereas SCF augmented insulin contents / DNA as well as islet DNA contents . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In order to examine the expression pattern of the NGF tyrosine kinase receptor during embryogenesis , we cloned a full length cDNA encoding chick trkA ( ctrkA ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The R 3 peptide had no effects on cell survival , cell binding or uptake of [ 125 ] NGF , affinity cross linking of [ 125 ] NGF to p 75 ( NGFR ) or trkA monomers and homodimers , of NGF mediated trkA monomer tyrosine phosphorylation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Synchronous onset of NGF and TrkA survival dependence in developing dorsal root ganglia . ^^^ The situation is complex , however , in that NT 3 ( / ) mutant mice show far greater neuron loss than mice deficient in the NT 3 receptor TrkC , suggesting that NT 3 may support many DRG neurons via actions on the NGF receptor TrkA . ^^^ To assess the possibility of ligand receptor cross talk as a developmental mechanism , we have compared the onset of survival dependence of lumbar DRG neurons on NT 3 , TrkC , NGF , and TrkA signaling in mice deficient in these molecules as a result of gene targeting . ^^^ The onset of survival dependence on NGF and TrkA signaling is concurrent and of equal magnitude at E13 . 5 , demonstrating that NT 3 alone does not support DRG neurons via TrkA , nor can NT 3 compensate for the loss of NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Since NGF exerts its effects via p75NTR and TrkA receptors coexpressed in vast majority of these neurones and down regulated without NGF treatment after injury , in this study we aimed to examine how does the lesion to the cholinergic tracts affect distribution of both types of receptor proteins in damaged fibres . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Of particular interest was the rapid phosphorylation ( by 1 min ) of the high affinity NGF ( TrkA ) receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Monoclonal antibody ( mAb ) 5C3 directed against human p 140 TrkA is a structural and functional mimic of nerve growth factor ( NGF ) and an artificial receptor agonist . mAb 5C3 binds in the NGF docking site and , like NGF , it promotes TrkA internalization , TrkA and phosphatidylinositol 3 kinase tyrosine phosphorylation , and increased transformation of TrkA expressing fibroblasts . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
While trkA and trkC mRNAs were expressed from stage 1 onwards , NGF and NT 3 mRNAs were expressed only at stages 3 and 5 , respectively . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Our results showed that whereas inhibiting Trk receptor phosphorylation abolishes NGF rescue of serum deprived PC 12 cells from apoptosis , TrkA suppression with antisense oligonucleotides did not . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) added to SH SY5Y cells stably transfected with the NGF receptor TRK A ( SH SY5Y / trk ) induces a similar differentiated phenotype . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF action was mediated through the TrkA receptor , in which messenger RNA ( mRNA ) was easily detected in UT 7 cells by Northern blot . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To test the molecular nature of the NGF receptor responsible for the ability of NGF to rescue septal cholinergic neurons following axotomy , we infused polyclonal antibodies that act as specific agonists of trkA ( RTA ) into the lateral ventricle of fimbria fornix lesioned animals . ^^^ These findings suggest that antibody induced trkA activation is sufficient to mediate NGF promoted survival of axotomized cholinergic neurons in vivo . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The contribution of nerve growth factor ( NGF ) to inflammatory hyperalgesia potentially could be mediated by any of the three peripheral cell types that express trkA , the high affinity NGF receptor : inflammatory cells , sympathetic neurons , and primary sensory neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The trkA specific ligand NGF has also been shown to activate the non tyrosine kinase receptor p 75 , a member of the tumour necrosis factor ( TNF ) receptor and Fas ( APO 1 / CD95 ) family . ^^^ Here we report that , early in development , endogenous NGF causes the death of retinal neurons that express p 75 but not trkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This study examines how the family of neurotrophin receptor tyrosine kinases ( Trks ) participates in the regeneration and replacement of olfactory neurons within the adult rat olfactory neuroepithelium . mRNA and protein products representing the high affinity nerve growth factor ( NGF ) receptor Trk A , its family members Trk B and Trk C , and the low affinity NGF receptor ( INGFR ) are all detected within both mature and regenerating olfactory neuroepithelium and within primary cultures of olfactory neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The patterns of NGF and trkA mRNA expression were very similar and were localized to the external part of the inner nuclear layer on the border with the outer plexiform layer and corresponded to the localization of horizontal cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have found evidence that part of the survival promoting activity of GM 1 is dependent on the presence , dimerization , and activation of the Trk NGF receptor tyrosine kinase and that GM 1 causes a detectable increase in Trk receptor autophosphorylation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Interestingly , LAR PTPs are phosphorylated on tyrosine in a TrkA dependent manner , and their association with the cadherin catenin complex is reduced in cells treated with NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We determined the expression of NGF and the neurotrophin receptors p 75 and trk in the somatosensory and motor cortices of mature rats with immunohistochemical techniques . ^^^ Sections of mature rat cortex were processed immunohistochemically with primary antibodies directed against NGF , p 75 , or trk . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immunolabelling for TrkA known to mediate biological effects of NGF and for GFAP to identify astroglial cells as a one of presumed source of postinjury produced factors was carried out on adjacent sections to establish the relation between expression of these proteins . ^^^ In control hippocampus NGF IR and TrkA IR were localized in neurons and / or neuropil . ^^^ The distribution pattern of NGF , TrkA and GFAP overlapped suggesting that reactive astrocytes may not only produce NGF but also may become responsive to this neurotrophin . ^^^ Zones of extensive NGF and TrkA astroglial expression corresponded to areas of axonal dendritic rearrangements reported earlier . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In neuronal cells , such as PC 12 , Shc has been shown to be involved in Ras dependent MAP kinase activation following Trk receptor stimulation with NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Dose response curves on cells expressing full length trkA were identical for NGF and NT 3 ( 0 . 1 ng / ml 50 ng / ml ) while cells expressing leucine rich motif ( LRM ) minus receptors required high concentrations of NT 3 ( 50 ng / ml ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To elucidate the contribution of the Trk family of tyrosine kinases to the phosphorylation events induced by NGF , we identified gp140trk in human B cells and in human B cell lines . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkC , the high affinity NT 3 receptor , and trkA , the high affinity NGF receptor , are both expressed from the early OLP through the mature OL stage . ^^^ Our data demonstrate the presence of functional trkA and trkC in developing OLs and indicate that both NGF and NT 3 have a broad spectrum of developmental actions on cells of the OL lineage . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The actions of nerve growth factor ( NGF ) are mediated by two receptor proteins , trk and p 75 . ^^^ Recent evidence indicates that NGF upregulates the expression of both trk and p 75 in responsive neurons including rat dorsal root ganglion ( DRG ) neurons . ^^^ Axotomy by disconnecting the neuron from its source of target derived NGF is predicted to lead to the downregulation of trk and p 75 expression . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Compared to controls ( n = 6 ) , CET rats ( n = 6 ) appeared to have significantly higher band intensity ( P < 0 . 01 ) of trk B like protein at about 145 kDa , which suggests an up regulation of trk B like proteins to compensate the compromised level of certain subset ( i . e . , BDNF or NT 4 / 5 , but not NGF ) of neurotrophins in cortex . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In contrast to p 75 , the NGF high affinity receptor trkA was little affected in sympathetic neurons by depletion of endogenous NGF for 2 weeks . ^^^ These results indicate that endogenous NGF is required in sympathetic ganglia for the expression of p 75 but not trkA in neurons , but for the down regulation of p 75 in glia . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immunoreactivity for acetylcholinesterase and low ( p 75 ) and high affinity ( TrkA ) NGF receptors was dense in NGF producing grafts but absent in control grafts . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Besides increasing choline acetyltransferase ( ChAT ) activities , nerve growth factor ( NGF ) strikingly induced trkA gene expression in a time and NGF concentration dependent manner . ^^^ Therefore , NGF might play a critical role in trkA gene expression during the development of basal forebrain cholinergic neurons . ^^^ Some neurotrophic factors increased ChAT activities to the same degree as NGF , whereas they did not stimulate trkA mRNA expression so potently . ^^^ NT 3 plus K252b promotes the tyrosine phosphorylation of TrkA in PC 12 cells and increases ChAT activity in cultured basal forebrain cholinergic neurons like NGF ( Knusel et al . , J Neurochem 59 : 715 722 , 1992 ) . ^^^ These results suggested that the expression of trkA mRNA is regulated directly by its specific ligand NGF , rather than neurotrophic effects upon basal forebrain cholinergic neurons and that the up regulation is connected to a molecular event initiated by the binding of NGF to the TrkA receptor . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
However , IL 6 alone failed to elicit neurite outgrowth in PC 12 cells and instead required low levels of Trk / NGF receptor tyrosine kinase activity to induce neuronal differentiation . ^^^ The cooperating Trk signal could be provided by either overexpression of Trk or exposure to low concentrations of NGF . ^^^ IL 6 and Trk / NGF synergized in enhancing tyrosine phosphorylation of the Erk 1 mitogen activated protein kinase and in activating expression of certain NGF target genes . ^^^ Moreover , our results demonstrate that a Trk receptor specific cellular response can be achieved in the absence of NGF through amplification of its basal signaling activity by the IL 6 receptor system . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In this article we compare the mRNA levels for neurotrophins ( NGF , BDNF , NT 3 , NT 4 ) and their high affinity receptors ( trkA , trkB , trkC ) in cultures enriched in specific glial types , such as microglia , type 1 astroglia , and cells of the O / 2A lineage ( type 2 astroglia and oligodendroglia ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the striatum , despite the loss of high affinity NGF binding previously reported , no loss of TrkA was observed . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
PC12EN lacked receptors for EGF and both the p 75 and trk NGF receptors , while FGF receptor expression was maintained . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) acts through the receptor tyrosine kinase trkA to serve as a trophic factor for cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band . ^^^ We have previously shown that the neuronal isoform of nitric oxide synthase ( NOS ) is selectively expressed in a large fraction of trkA expressing cholinergic neurons in these brain regions in the adult rat , and that NGF induces the expression of neuronal NOS in these cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF specifically activates the receptor trkA , initiating a signal transduction cascade which ultimately blocks cell death . ^^^ NGF binding to mature oligodendrocytes expressing the p 75 neurotrophin receptor , but not trkA , resulted in a sustained increase of intracellular ceramide and c Jun amino terminal kinase ( JNK ) activity , which are thought to participate in a signal transduction pathway leading to cell death . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In contrast , the level of trkA , the NGF receptor , regulates these properties in caudate putamen cholinergic neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Comparisons of the extracellular domains showed some amino acid motifs of putative NGF binding function to be well conserved in chicken TrkA . ^^^ This upregulation of trkA was corroborated by subsequent NGF stimulated fiber outgrowth . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Expression of mRNAs for neurotrophic factors ( NGF , BDNF , NT 3 , and GDNF ) and their receptors ( p75NGFR , trkA , trkB , and trkC ) in the adult human peripheral nervous system and nonneural tissues . ^^^ The steady state mRNA levels of the four neurotrophic factors of nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , neurotrophin 3 ( NT 3 ) and glial cell line derived neurotrophic factor ( GDNF ) and their receptors ( p75NGFR , trkA , trkB and trkC ) in the adult human peripheral nervous system ( PNS ) as well as nonneural tissues were examined using quantitative reverse transcription polymerase chain reaction ( RT PCR ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To determine if this in vitro switch in neurotrophin responsiveness is physiologically relevant , we studied the timing of neuronal death in the trigeminal ganglia of embryos that are homozygous for null mutations in the trkA , trkB and trkC genes , which encode receptor tyrosine kinases for NGF , BDNF and NT 3 , respectively . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Gene transcripts for the high affinity NGF receptor trkA were found exclusively in non germ cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Activation of trkA , the nerve growth factor ( NGF ) tyrosine kinase receptor , has been recently implicated in the process of mammalian ovulation . ^^^ During the hour preceding follicular rupture , a marked increase in trkA and NGF gene expression occurs in thecal interstitial cells of the ovary . ^^^ Immunoneutralization of NGF actions or pharmacological blockade of trkA transducing activity inhibits ovulation , suggesting that activation of the NGF trkA complex in nonneural cells of the periovulatory follicle is a physiological component of the ovulatory cascade . ^^^ We now report that NGF induced activation of trkA receptors in isolated ovarian thecal cells disrupts cell to cell communication by affecting the functional integrity of gap junctions . ^^^ Bovine thecal cells expressing trkA receptors , but not cells lacking the receptors , respond to NGF with a reduction in the transfer of calcein , a fluorescent dye that passes through gap junctions . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF does not result in TrkA phosphorylation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Members of the neurotrophin family activate different receptors that belong to a class of receptor tyrosine kinases known as `` Trks . ' ' For example , NGF is the specific ligand of TrkA , while BDNF activates TrkB . ^^^ Our findings revealed that , although BDNF is absolutely conserved in mammals , substitution of several small variable regions from NGF into the BDNF backbone did not lead to significant loss in TrkB activity or gain in TrkA activity . ^^^ On the other hand , critical elements for TrkA activation might be located within the amino terminal half of the mature NGF molecule . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Up regulation of NGF , trkA , Fas , down regulation of bcl 2 , and induction of apoptosis by propentofylline in human glioma cell lines ] . ^^^ After administration of PPF into the glioma cell lines , we investigated morphological changes and gene and protein expression of NGF , trkA , Fas and bcl 2 by using GFAP staining . ^^^ The mRNA and protein expression of NGF , trkA and Fas increased , but expression of bcl 2 decreased . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Postnatal changes in the expression of the trkA high affinity NGF receptor in primary sensory neurons . ^^^ In development approximately 70 80 % of dorsal root ganglion ( DRG ) cells are dependent on nerve growth factor ( NGF ) for their survival , while in the adult only some 40 % of DRG cells express the high affinity NGF receptor , trkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
It is speculated that NT 5 exerts its action either directly on the trkA receptor , as with NGF or alternatively through trkB receptors located on sympathetic efferents or on small diameter afferents . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
It is , however , unknown whether other homologous neurotrophins also act outside the nervous system , and whether activation of basophils by NGF requires interaction with trk tyrosine kinase receptors , the low affinity NGF receptor ( LNGFR ) , or both . ^^^ Brain derived neurotrophic factor , which interacts with trkB , was inactive at concentrations up to 1000 ng / ml ( > 30 , 000 fold lower potency than NGF ) , while neurotrophin 3 , which is thought to interact with trkC , trkB , and more weakly with trk , induced a threshold effect at 300 ng / ml ( approximately 10 , 000 fold lower potency ) , demonstrating that 1 ) the LNGFR can not deliver a direct signal ; and 2 ) basophils do not express functional trkB and trkC receptors . ^^^ These data demonstrate that human blood basophils express functional trk receptors that do not require the participation of LNGFR , and that , among the neurotrophin family , NGF is unique in priming basophils . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Human recombinant NGF mediated phosphorylation of a 140 kDa Trk NGF receptor in the TSU pr 1 cell line was inhibited by treatment with 100 nM K252a . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
However , coaddition of K 252b ( EC 50 of approximately 2 nM ) with 10 100 ng / ml NT 3 led to incorporation of [ 3H ] thymidine in trkA expressing cells to a level induced by optimal concentrations of nerve growth factor ( NGF ) . ^^^ K 252b did not potentiate submaximal doses of NGF , or maximal doses of brain derived neurotrophic factor ( BDNF ) or neurotrophin 4 / 5 ( NT 4 / 5 ) in trkA expressing cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Here , we examined the effects of nerve growth factor ( NGF ) and its cognate receptor ( Trk or TrkA ) on the survival of a common childhood brain tumor , i . e . , medulloblastoma , a tumor that resembles CNS neuroepithelial progenitor cells . ^^^ Surprisingly , NGF treated medulloblastoma cells expressing the TrkA receptor ( D283trk and DAOYtrk cells ) grown in the presence or absence of serum underwent massive apoptosis , but similar treatment did not induce apoptosis in wild type uninfected cells , cells expressing an empty vector , or cells expressing the TrkC receptor . ^^^ Significantly , NGF induced apoptosis in D283trk and DAOYtrk cells can be inhibited by anti NGF antibodies and by K 252a , an inhibitor of TrkA tyrosine phosphorylation and mimicked by high concentrations of NT 3 . ^^^ These findings suggest that a NGF / TrkA signal transduction pathway could activate apoptotic cell death programs in CNS neuroepithelial progenitor cells and in childhood brain tumors . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have examined early events in the membrane traffic of NGF and its receptor , gp 140 ( TrkA ) ( TrkA ) , in PC 12 cells . ^^^ NGF induced rapid and extensive endocytosis of TrkA in these cells , and the receptor subsequently moved into small organelles located near the plasma membrane . ^^^ After NGF treatment , NGF was bound to TrkA in endocytic organelles , and TrkA was tyrosine phosphorylated and bound to PLC gamma 1 , suggesting that these receptors were competent to initiate signal transduction . ^^^ These studies raise the possibility that NGF induces formation of signaling endosomes containing activated TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The mechanism ( s ) underlying nerve growth factor ( NGF ) mediated rescue of neurons from apoptosis is poorly understood , although it is well established that the high affinity NGF receptor ( TrkA ) plays a pivotal role in mediating NGF effects . ^^^ These results indicate that NFkappaB function is essential to maintain PC 12 cell survival and to permit NGF mediated rescue , consistent with the idea that signaling elements potentially associated with both TrkA and p75NGFR are involved in the regulation of apoptosis . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Treatment of NIH 3T3 cells expressing TRKA with PD 98059 dramatically reversed the complete inhibition of growth of these cells caused by NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Since trkA has not been detected in the avian sympathetic ganglia until later in development , we suggest that these early effects of exogenous NGF may be mediated by the low affinity neurotrophin receptor , p 75 , which is expressed from neural crest migration stages . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF and neurotrophin 3 both activate TrkA on sympathetic neurons but differentially regulate survival and neuritogenesis . ^^^ Both NT 3 and NGF induce similar sustained , long term activation of TrkA , while NGF is 10 fold more efficient than NT 3 in mediating acute , short term TrkA activity . ^^^ At similar acute levels of TrkA activation , NT 3 still mediates neuronal survival two to threefold less well than NGF . ^^^ On the basis of these data , we suggest that NGF and NT 3 differentially regulate the TrkA receptor both with regard to activation time course and downstream targets , leading to selective regulation of neuritogenesis and survival . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Paravertebral sympathetic neurons and chromaffin cells of the adrenal medulla share an ontogenetic origin , responsiveness to NGF , and expression of TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Using sequential immunohistochemistry with antibodies that recognize preferentially TrkA , the specific receptor for NGF , and with antibodies directed against choline acetyltransferase we analyzed the expression of neurotrophin receptors in cholinergic neurons from control and AD brains . ^^^ Taken in conjunction with our previously published report of loss of high affinity NGF binding in the striatum of AD patients , our results suggest a reduced expression of TrkA , the specific receptor for NGF , on striatal cholinergic neurons in AD . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The recent demonstration that TrkA , the essential component of high affinity NGF receptors , is expressed not only at the distal fields ( terminals and distal axons ) but also at the proximal fields ( cell bodies , dendrites , and proximal axons ) of the basal forebrain cholinergic neurons has provoked renewed interest in this problem . ^^^ Thus , it will be crucial to clarify whether or not the TrkA receptors on the somatodendritic fields of the NBM cholinergic neurons respond to exogenous NGF in order to support the rationale for site directed neurotrophic factor therapy in AD or other neurological disorders . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have studied the postnatal expression of neurotrophins , their cognate high affinity trk receptors and the low affinity NGF receptor ( p75LNGFR ) in the rat adrenal gland using RT PCR . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These results suggest that the NGF effect is mediated by the high affinity NGF receptor , Trk A and that neurotrophin binding to the low affinity neurotrophin receptor , p 75 ( NTR ) , alone does not affect the promoter activity . ^^^ This study examined the effect of NGF on the activity of the N methyl D aspartate receptor subunit 1 ( NMDAR 1 ) promoter / luciferase reporter constructs in PC 12 cells , which contain the high affinity TrkA receptor for NGF and the low affinity p 75 ( NTR ) receptor for neurotrophins . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This is not explained enough by the quantitative difference in the strength between TrkA and TrkB stimulation , because the level of BDNF stimulated tyrosine phosphorylation of TrkB was similar to that of TrkA stimulated with NGF in PC12 / TrkB cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Inhibition of neuronal differentiation is accompanied by significant changes in the protein and mRNA expression pattern of the high affinity NGF receptor ( trkA ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
K 252a inhibits the effect of NGF on p 140 ( trk ) cells but not on p 75 ( NGFR ) cells ; brain derived neurotrophic factor stimulates calcium uptake in p 75 ( NGFR ) cells but not in p 140 ( trk ) cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Three clones of PC 12 cells that differ with respect to their nerve growth factor ( NGF ) receptors were examined : wild type PC 12 cells that have both trkA and p75LNTR receptors ; the MR 1 clone that possesses a normal trkA receptor and a truncated form of p75LNTR without the extracellular NGF binding part ; and a new PC 12 variant , called 5 clone , that is partly characterized here . ^^^ It is concluded that although trkA is required for differentiation in response to NGF in PC 12 cells , the concomitant stimulation , by NGF , of p75LNTR may affect phospholipase C and AP 1 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
RNA analysis revealed that NGF mRNA was expressed in the pregnant uterus on day 7 . 5 p . c . , mainly in the decidua , but it could not be detected in the EPC . p75NGFR mRNA was expressed in the EPCs , whereas TrkA mRNA was not detected in the placental tissues throughout day 7 . 5 to 10 . 5 p . c . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In this report , we define precisely the residues in human NGF responsible for NGF biological activity and binding specificity to the neurotrophin receptor TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In this paper we report a time course study of development of experimental allergic encephalomyelitis in Lewis rats , by monitoring neuroendocrine regulation of the hypothalamus pituitary adrenal axis through corticotropin releasing hormone mRNA expression , inflammatory cellular infiltrate , macrophagic and neuronal nitric oxide synthase , nerve growth factor ( NGF ) , and NGF p 75 and trkA receptors in the brain and spinal cord . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To examine their roles in the TRK NGF receptor , these residues ( Tyr 670 , Tyr 674 , and Tyr 675 ) were mutated singly and in all combinations to phenylalanine and stably expressed in Trk deficient PC12nnr5 cells . ^^^ Our findings stress the importance that expression levels play in assessing the consequences of receptor mutations and that all three activation loop tyrosines have roles regulating both overall and specific NGF mediated signaling through TRK . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
For nerve growth factor ( NGF ) , these are p75NTR ( p 75 ) and p140trk ( referred to as trk or trkA ) , which binds both BDNF and neurotrophin ( NT ) 4 / 5 , and trkC receptor , which binds only NT 3 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Using an oxidation sensitive compound , dihydrorhodamine , we measured ROS formation in a central nervous system derived neuronal cell line ( GT 1 1 trk ) and in superior cervical ganglion neurons , both of which express the transmembrane NGF receptor tyrosine kinase , trkA . ^^^ There was enhanced production of ROS in both cell types in the absence of NGF that was rapidly inhibited by application of NGF ; complete inhibition of ROS generation in GT 1 1 trk cells occurred within 10 min . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This down regulation does not occur in PC12nnr5 cells , which lack the p 140 ( trk ) NGF receptor . ^^^ However , in PC12nnr5 cells stably transfected with p 140 ( trk ) , the NGF induced heterologous down regulation of EGF receptors is reconstituted in part . ^^^ These results strongly suggest a p 140 ( trk ) , Ras and Src dependent mechanism of NGF induced down regulation of EGF receptors and separate this process from NGF induced neurite outgrowth in PC 12 cells . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Both cortical and basal forebrain explant cultures express the NGF receptor , TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Transient tyrosine phosphorylation of the Trk / NGF receptor was detected at 5 15 min after NGF treatment in control cells , but not detected in the GnT 3 gene transfected cells despite the intact binding of NGF to the cells . ^^^ Moreover the dimerization of Trk with NGF treatment was not induced in the GnT 3 transfectant as compared with the dimerization seen in control cells . ^^^ These results indicate that overexpression of GnT 3 gene in PC 12 cells affects some functions of glycoprotein receptors such as Trk by alteration of N glycan structures , and results in changes in the intracellular signaling pathway of tyrosine phosphorylation modified by NGF . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
LIP 1 , a 29 amino acid ( aa ) peptide , and LIP 2 , a 38aa peptide , corresponding to sequences within the nerve growth factor ( NGF ) precursor that are flanked by basic amino acid processing sites , were shown to be present in the rat intestine and to induce in PC 12 cells several early cellular events , such as F actin rearrangement and tyrosine phosphorylation of the Trk protein . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The binding sites of neurotrophin 3 ( NT 3 ) and nerve growth factor ( NGF ) to their preferred receptors trkC and trkA , respectively , were previously determined by mutational analyses . ^^^ These and other studies showed that trkA can discriminate between NGF and NT 3 primarily by recognition of their N terminal residues . ^^^ Exchange of NGF residues at positions 18 , 20 , 23 , 29 , 84 , and 86 by their NT 3 counterparts resulted in NGF variants that bound to trkC , while maintaining their affinity to trkA , and were able to induce autophosphorylation and differentiation of PC 12 cells expressing trkC . ^^^ The results demonstrate the importance of nonconserved residues of the central beta strand bundle region for the interaction of NT 3 with trkC and emphasize the different mechanism of specificity determination that is employed in the NT 3 / trkC and NGF / trkA ligand / receptor pairs . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) , signaling through its receptor tyrosine kinase , TrkA , is required for the survival of all small and many intermediate sized murine dorsal root ganglion ( DRG ) neurons during development , accounting for 80 % of the total DRG population . ^^^ Surprisingly , NGF / TrkA dependent neurons include a large population that does not express TrkA in adult mice ( Silos Santiago et al . , 1995 ) . ^^^ Because the period of TrkA down regulation corresponds with a critical period during which nociceptive phenotype can be altered by NGF ( see Lewin and Mendell [ 1993 ] Trends Neurosci . 16 : 353 359 ) , we examined whether NGF modulates the down regulation of TrkA . ^^^ Surprisingly , neither NGF deprivation nor augmentation altered the extent of TrkA down regulation . ^^^ All DRG neurons that require NGF for survival express TrkA during embryogenesis , and many continue to express TrkA during a postnatal period when neuronal phenotype is regulated by NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We conclude that BDNF promotes survival in part via its TrkB receptor , whereas there is an additional pathway promoting survival and elevating c Jun evoked by both NGF and BDNF via a non Trk receptor . . ^^^ No TrkA is detected , although p 75 ( NTR ) protein is expressed and NGF induces depolarization dependent elevation of c Jun levels . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immunohistochemistry was consistently negative for GFAP , trkA ( the high affinity receptor for NGF ) , CD 4 , CD 8 , and a macrophage specific marker ( Ox 41 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Our findings suggested that NGF / trkA may potentially be involved in the RA induced differentiation of leukemia cells . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The high affinity receptor for nerve growth factor ( NGF ) , trkA , is a receptor linked tyrosine kinase . ^^^ The binding of NGF to trkA , depending on the context of its environment , can cause beneficial or deleterious responses in the target cells . ^^^ On the other hand , the activation of trkA by NGF in other cells has been implicated in several pathologies including inflammation induced hyperalgesia and several cancers . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These neurons , which are located in the nucleus prepositus hypoglossi ( NPH ) , spinal vestibular nucleus , cochlear complex , and gigantocellular and paragigantocellular nuclei of the reticular formation , express functional receptors for NGF and up regulate the expression of trkA receptors after injection of NGF into targets . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
A series of 3 , 9 disubstituted [ ( alkylthio ) methyl ] and ( alkoxymethyl ) K 252a derivatives was synthesized with the aim of enhancing and separating the neurotrophic properties from the undesirable NGF ( trk A kinase ) and PKC inhibitory activities of K 252a . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
GM 1 enhances nerve growth factor ( NGF ) stimulated neuritogenesis and prevents apoptotic death of PC 12 cells ; both may be due to enhancement of TrkA dimerization . ^^^ In this study , we examined the effect of GM 1 on NGF induced TrkA dimerization in Trk PC 12 ( 6 24 ) cells . ^^^ NGF increased tyrosine phosphorylation of the 140 kDa protein ( TrkA monomer ) , and preincubation with GM 1 potentiated this effect . ^^^ Adding the protein cross linker bis ( sulfosuccinimidyl ) suberate with NGF resulted in the appearance of two major bands ( 220 and 330 kDa ) when probed with antibodies against TrkA or phosphotyrosine , and GM 1 also enhanced this effect . ^^^ Our results suggest that GM 1 is augmenting the effects of NGF on PC 12 cells by enhancing the dimerization and activation of the TrkA receptor . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Quantitative in situ hybridization was used to examine the expression of mRNA for nerve growth factor ( NGF ) and its receptors , p140Trk ( TrkA ) and p75LNGFR ( LNGFR ) , in different brain regions of adult ( 3 month old ) and aged ( 27 month old ) Wistar rats . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Embryonic precursor cells that express Trk receptors : induction of different cell fates by NGF , BDNF , NT 3 , and CNTF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF binds to two classes of cell surface receptors , the protein tyrosine kinase TrkA and the smaller p 75 receptor lacking intrinsic catalytic activity . ^^^ It has been suggested that both receptors are required for NGF high affinity binding , although TrkA appears to be sufficient for transducing most of the biological effects of NGF . ^^^ In this study , we have investigated functional roles of p 75 using a purified triple mutant NGF ( triNGF ) deficient in p 75 binding but retaining significant TrkA binding and activation . ^^^ The mutant was found to be as potent as wild type NGF at promoting survival of serum deprived TrkA expressing fibroblasts . ^^^ These results support a ligand dependent modulatory role for p 75 in NGF mediated neuron survival consistent with p 75 functioning as a TrkA regulator and / or signaling receptor . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In vitro studies show that keratinocytes express both NGF and its high affinity receptor , trkA , and that NGF may increase keratinocyte proliferation and its own expression via an autocrine loop . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Previous studies have shown that activation of phosphatidylinositol 3 kinase ( PI 3 kinase ) by NGF via the TrkA receptor tyrosine kinase protects PC 12 cells from serum deprivation induced apoptosis . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
A role for the local activation of the high affinity NGF receptor trkA was suggested by a strong inhibition of the turning response by ( 1 ) the addition of an antibody against the extracellular portion of trkA , ( 2 ) the elevation of the background concentration of NGF to saturate trkA , or ( 3 ) the presence of a concentration of the drug K252a that inhibits trkA activation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Several in vitro and in vivo studies have led to the widely accepted view that NT 3 is required for sympathetic neuroblast survival , induction of TrkA expression and the acquisition of NGF dependence . ^^^ However , we show that the number of neurons and the levels of trkA and p 75 mRNAs in the superior cervical sympathetic ganglion ( SCG ) of NT 3 / mouse embryos increase normally up to E 16 , 2 days after SCG neurons start responding to NGF . ^^^ These results show that the neurotrophin survival requirements of SCG neurons do not switch from NT 3 to NGF during development and that NT 3 is not required for the expression of TrkA and p 75 and the acquisition of NGF dependence . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Intracellular application of a phosphopeptide , Trk 490 , which prevents the binding of the adaptor protein shc to the activated NGF receptor , so blocking p 21 ras activation , reduced 1 ( max ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) acts through trkA receptors to serve as a trophic factor for cholinergic neurones in the medial septal nucleus ( MSN ) and vertical limb of the diagonal band ( VDB ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These neurons are considered to be maintained by neurotrophins such as nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , and neurotrophin 3 ( NT 3 ) and trk family of neurotrophin receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Ginsenoside Rb 1 regulates ChAT , NGF and trkA mRNA expression in the rat brain . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Limiting consideration to the role of p75NTR in cell death , a theory is proposed that is based on the following postulates : ( 1 ) that p75NTR displays a pro apoptotic intrinsic ( ligand independent , Trk independent ) receptor effect ( IRE ) , which is inhibited by ligand binding ; ( 2 ) that p75NTR and TrkA exhibit mutual repression of signaling ; and ( 3 ) that p75NTR and TrkA are required for the efficient generation of high affinity NGF binding sites . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
It has been hypothesized that the diminished transport of nerve growth factor ( NGF ) seen within cholinergic basal forebrain ( CBF ) neurons in Alzheimer ' s disease ( AD ) results from a defect in the expression of its high affinity trkA receptor . ^^^ The present study used an anti human trkA specific monoclonal antibody ( mAb 5C3 ) that recognizes the NGF docking site , combined with quantitative optical densitometry , to evaluate whether expression of the trkA protein is altered within the nucleus basalis and its cortical projection sites in AD . ^^^ The decrease in trkA protein in conjunction with our recent observations that the message for trkA is reduced within individual CBF neurons in AD supports the concept that defects in the production and / or utilization of the trkA receptor may be a key event mediating degeneration of NGF responsive CBF neurons in this disease . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
However , we observed that NGF applied locally to distal axons of rat sympathetic neurons in compartmented cultures produced increased tyrosine phosphorylation of trkA in cell bodies / proximal axons within 1 min . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Expression of a murine temperature sensitive ( ts ) p 53 mutant in PC 12 cells overexpressing trk ( a model system to analyse cellular differentiation and signal transduction induced by NGF ) induces morphological changes in the absence of NGF stimulation at 32 degrees C but not at 37 degrees C . ^^^ However , transfection of ts p 53 into these cells induces trk phosphorylation at 32 degrees C in the absence of NGF stimulation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) receptor mediated signaling was studied using specific monoclonal antibodies ( mAbs ) as ligands that discriminate between the receptors TrkA and p 75 . mAb induced trophic signals were compared with the signals of the natural ligand NGF . ^^^ In contrast , in cells expressing p 75 receptors singly ( TrkA p 75 ( + ) ) , binding with mAb MC 192 or NGF causes very limited or no trophic effects . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF binding to the high affinity tyrosine kinase ( TrkA ) receptors initiates second messenger signalling cascades , one of which includes the activation of phosphoinositide 3 kinase ( PI 3 kinase ) . ^^^ As PI 3 kinase is present in both neuronal populations , this suggests that the Wortmannin sensitive isoform of PI 3 kinase ( p 110 ) is essential in sympathetic neurones both for survival and for NGF TrkA receptor complex trafficking . ^^^ As sensory neurones also depend on NGF for their developmental survival and endocytose and retrogradely transport the NGF TrkA receptor complex , this population of neurones may either recruit a different isoform of PI 3 kinase or utilize PI 3 kinase independent signalling pathways for these cellular functions . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Molecular modeling studies predict that Zn2+ binding to NGF will induce structural changes within domains of this neurotrophin that participate in the recognition of TrkA and p75NTR . ^^^ We demonstrate here that Zn2+ alters the conformation of NGF , rendering it unable to bind to p75NTR or TrkA receptors or to activate signal transduction pathways and biological outcomes normally induced by this protein . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To identify nerve growth factor ( NGF ) target cells in normal and pathologic human lymphoid tissues , we have studied the expression of the low affinity NGF receptor ( p75LNGFR ) and the high affinity tropomyosin related kinase NGF receptor ( TrkA ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have investigated the effect of capsaicin pretreatment ( 50 mg kg ( 1 ) s . c . ) on substance P , preprotachykinin ( PPT ) mRNA , and nerve growth factor ( NGF ) , plus its high affinity receptor , trkA , in adult rats with adjuvant arthritis . ^^^ NGF levels in sciatic nerve and foot skin as well as DRG trkA mRNA were unaltered after 21 days arthritis suggesting that NGF may not play a role in chronic inflammation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Reproducible standard curves were generated with an EC 50 of approximately 16 ng / ml NGF for gD . trkA KIRA , 11 ng / ml for NT4 / 5 and 20 ng / ml for BDNF in gD . trkB KIRA , and 9 . 4 ng / ml for NT 3 in gD . trkC KIRA . ^^^ When the gD . trkA KIRA assay was used to quantify serum NGF or NT 3 following administration to rats , the assay agreed well with currently existing ELISA assays . ^^^ When the gD . trkA KIRA assay was used to test several NGF variants , as well as NGF stability samples , the capacity of the assay to quantify ligand bioactivity compared well with the more widely used radioreceptor binding and PC 12 cell survival assays . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This study examined whether ethanol exposure of the neonatal rat cerebellum altered the levels of either NGF or the expression of p 75 and trkA , which are two components of the NGF receptor . ^^^ Immunohistochemical labeling techniques indicated that both the p 75 and trkA NGF receptors were expressed on Purkinje cell dendrites in the developing cerebellum , with posterior lobules expressing higher levels of p 75 and trkA NGF receptor , compared with anterior lobules . ^^^ Ethanol exposure of neonatal rats reduced the expression of both p 75 and trkA NGF receptors on the Purkinje cell dendrites . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Pulpal fibroblasts express nerve growth factor ( NGF ) and the low affinity p 75 neurotrophin receptor , their sensory nerve fibers express p 75 and trk A , and pulpal sympathetic fibers lack p 75 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These findings suggest that the EGF and NGF ( TrkA ) receptor can utilize Shc in different ways to promote their activity . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Moreover , in a subpopulation of DRG neurons , the estrogen receptor is colocalized with high affinity ( trkA ) and low affinity ( p75NGFR ) receptors for nerve growth factor ( NGF ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This organelle is derived from endocytosis of the receptor tyrosine kinase for NGF , TrkA . ^^^ In vitro reactions containing semi intact PC 12 cells and ATP were used to enhance recovery of a novel organelle : small vesicles containing internalized NGF bound to activated TrkA . ^^^ They contained 10 % of the total bound NGF and almost one third of the total tyrosine phosphorylated TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Herein , we demonstrate that TrkAKi receptors show a decrease in the absolute amount of kinase activity relative to wild type TrkA , yet retain normal patterns of receptor tyrosine phosphorylation , as determined by phosphopeptide mapping studies , unlike TrkC ( Ki 14 ) . nnr 5 cell clones expressing TrkAKi receptors show a decrease in nerve growth factor ( NGF ) mediated SHC tyrosine phosphorylation and a loss of high affinity TrkA SHC interaction comparable to those expressing TrkC ( Ki 14 ) . ^^^ TrkAKi receptors internalize NGF comparable to wild type TrkA , but do not stimulate neurite outgrowth . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) treatment of rat PC 12 pheochromocytoma cells results in an increase in the tyrosine phosphorylation of the NGF receptor , TrkA , leading to differentiation to a neuronal phenotype . ^^^ The Src homology 2 domain containing PTPase SHP 2 was found to associate transiently with TrkA following receptor activation , reaching a peak after 1 min of NGF treatment and then decreasing rapidly . ^^^ This is the first demonstration that the association of SHP 2 with TrkA is induced by NGF and that this association leads to SHP 2 activation and tyrosine phosphorylation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To determine how elevated levels of a target derived neurotrophin might affect neuronal differentiation , we analysed trk expression in the trigeminal ganglion of transgenic mice that overexpressed nerve growth factor ( NGF ) in the skin . ^^^ These studies indicate that an increased level of target derived NGF affects the development of sensory neurons that in the adult express trkA or trkC , as well as neurons that do not express trk receptors . . ^^^ Increased levels of NGF caused a five fold increase in neurons expressing trkA mRNA and a two fold increase in neurons expressing trkC . ^^^ In contrast , cell size distribution in NGF transgenic mice was significantly divergent due in large part to hypertrophy of trkA neurons and , to a lesser extent , trkC neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We report the presence in rat spinal cord of a novel neuronal system expressing tyrosine kinase receptor ( trkA ) , the high affinity receptor for nerve growth factor ( NGF ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Furthermore , bFGF induced expression of the high affinity NGF receptor ( trkA ) gene . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In rodent models of diabetes , there are expression deficits in nerve growth factor ( NGF ) and in mRNA for its high affinity receptor , trkA , leading to decreased retrograde axonal transport of NGF and decreased support of NGF dependent sensory neurons , with reduced expression of their neuropeptides , substance P and calcitonin gene related peptide ( CGRP ) . ^^^ In regenerating nerves after experimental crush injury , expression of NGF in the nerve trunk is increased in diabetes to a greater extent than in controls , but this is offset by a greater reduction in the neuronal expression of trkA in dorsal root ganglia of diabetic rats . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF achieves inhibition of activity of these cyclin dependent kinases by signalling through the TrkA receptor to the tumor suppressor protein p 53 and then to p21 / WAF1 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
An NGF TrkA mediated retrograde signal to transcription factor CREB in sympathetic neurons . ^^^ Internalization of NGF and its receptor tyrosine kinase TrkA , and their transport to the cell body , were required for transmission of this signal . ^^^ Thus , an NGF TrkA complex is a messenger that delivers the NGF signal from axon terminals to cell bodies of sympathetic neurons . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TRKA , a receptor tyrosine kinase cloned from a human colon cancer was later found to be expressed in the nervous system and phosphorylated in response to NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF stimulation of HMC 1 cells induced tyrosine phosphorylation of TrkA protein , increased expression of the early response genes c fos and NGF 1 A , and activation of ERK mitogen activated protein ( MAP ) kinase , results which indicate that TrkA receptors in HMC 1 cells are fully functional . ^^^ Moreover , preparations of human umbilical cord blood derived immature mast cells not only expressed mRNA transcript and protein for TrkA , but exhibited significantly higher numbers of chymase positive cells after the addition of NGF to their culture medium for 3 weeks . ^^^ In addition , HMC 1 cells expressed mRNAs for NGF , brain derived neurotrophic factor ( BDNF ) , and neurotrophin 3 ( NT 3 ) , the cognate ligands for TrkA , TrkB , and TrkC , whereas NGF and BDNF transcripts were detectable in human umbilical cord blood mast cell preparations . ^^^ Taken together , our findings show that human mast cells express a functional TrkA receptor tyrosine kinase and indicate that NGF may be able to promote certain aspects of mast cell development and / or maturation in humans . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
METHODS : The expression of NGF and a transmembrane tyrosine kinase ( TrkA ) was evaluated by immunohistochemistry and flow cytometry analysis in five T ( H 0 ) , six T ( H 1 ) , and five T ( H 2 ) cell clones derived from human circulating mononuclear blood cells . ^^^ RESULTS : Our data have shown that in unstimulated conditions , human CD4+ T cell clones express both immunoreactivity for NGF and the TrkA NGF receptor irrespective of their cytokine profile . ^^^ CONCLUSIONS : Results obtained represent the first evidence of TrkA expression and NGF production and release in human CD4+ cell clones and suggest a possible functional role of NGF in modulating the immune and inflammatory network . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) , acting via the TrkA receptor , has been shown to regulate the survival and maturation of specific neurons of the peripheral nervous system . ^^^ Furthermore , exogenous NGF has potent actions on TrkA expressing cholinergic neurons of the basal forebrain ( BFCNs ) and striatum . ^^^ However , initial analysis of mice lacking NGF or TrkA revealed that forebrain cholinergic neurons were present in these animals through the fourth postnatal week . ^^^ Because of the potential effects of NGF / TrkA interactions on these developing neurons , we have analyzed quantitatively the striatal and basal forebrain cholinergic neurons in trkA knock out mice . ^^^ Our data suggest that , in the absence of NGF / TrkA signaling , striatal cholinergic neurons and BFCNs do not mature fully and that BFCNs begin to atrophy and / or die surrounding the time of target innervation . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Second , consistent with the various affinities for particular trk receptors , the elimination of NGF , BDNF , and NT 3 has an impact comparable to or more complex than the absence of their most specific high affinity receptors : trkA , trkB , and trkC , respectively . ^^^ Immunofluorescence with anti protein gene product 9 . 5 , anti 200 kDa neurofilament protein ( RT 97 ) , and anti calcitonin gene related product was used to label innervation in mystacial pads from mice with homozygous null mutations for nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , neurotrophin 3 ( NT 3 ) , neurotrophin 4 ( NT 4 ) , the three tyrosine kinase receptors ( trkA , trkB , trkC ) , and the low affinity nerve growth factor receptor p 75 . ^^^ Third , most types of afferents are dependent on a different combination of neurotrophins and receptors for their survival : reticular and transverse lanceolate afferents are dependent upon NT 3 , NGF , and trkA ; Ruffini afferents upon BDNF and trkB ; longitudinal lanceolate afferents upon NGF , trkA , BDNF , and trkB ; and Merkel afferents on NGF , trkA , NT 3 , trkC , and p 75 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Several mutagenesis studies , however , have localized the binding sites of the two NGF receptors , p 75 and TrkA , to other regions of the NGF molecule . ^^^ We found that point mutations within the 111 115 region , but not deletion of residues 116 120 , significantly decreased NGF bioactivity , as determined by TrkA tyrosine phosphorylation and neurite outgrowth from PC 12 cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Members of the nerve growth factor ( NGF ) family of neurotrophins bind to the second leucine rich motif ( LRM 2 ) within the extracellular domains of their respective receptors ( trkA , trkB , trkC ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
It is concluded that NGF and NT 3 use overlapping as well as separated regions for determination of specificities for their cognate receptors TrkA and TrkC , respectively . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the adult rat , BDNF mRNA and protein were found mainly in the subpopulation of cells that express the nerve growth factor ( NGF ) receptor trkA and the neuropeptide calcitonin gene related peptide ( CGRP ) . ^^^ NGF increased BDNF within the trkA / CGRP cells to the extent that almost 90 % of trkA cells contained BDNF mRNA after intrathecal NGF treatment , and 80 90 % of BDNF expressing cells contained trkA . ^^^ However , very few trkB cells expressed either BDNF mRNA or protein , and NGF did not increase BDNF expression in non trkA cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To determine if human mast cells express the NGF receptors , TrkA tyrosine receptor and the low affinity NGF receptor ( LNGFR ) , we first analyzed the mRNA expression by RT PCR of TrkA and LNGFR in a human mast cell line ( HMC 1 ) and in human mast cells cultured in the presence of stem cell factor . ^^^ Treatment of mast cells with NGF resulted in phosphorylation of TrkA on tyrosine residues as detected by immunoblotting with an antiphosphotyrosine antibody . ^^^ Thus , mast cells express functional TrkA and synthesize NGF , suggesting a mechanism by which NGF may act as an autocrine factor for human mast cells , and by which mast cells and nerves may interact . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have tested the role of glial cell line derived neurotrophic factor ( GDNF ) in regulating a group of putatively nociceptive dorsal root ganglion ( DRG ) neurons that do not express calcitonin gene related peptide ( CGRP ) and that downregulate the nerve growth factor ( NGF ) receptor tyrosine kinase , TrkA , after birth . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Similar enhancements were observed with NT 3 and NT 4 and with NGF despite the fact that hippocampal neurons lack TrkA receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) prevents apoptosis through stimulation of the TrkA receptor protein tyrosine kinase . ^^^ Hence , Gab 1 has a major role in connecting TrkA with PI 3 kinase activation and for the promotion of cell survival by NGF . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The reliability of this assay was first monitored by the differential expression of the NGF and NT 3 receptors trkA and trkC , as well as that of neuropeptides and calcium binding proteins . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the rat thymus , mRNA for TrkA ( an essential component of the NGF signal transducing receptor ) has been found primarily in stromal cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Because neurotrophins , a family of related polypeptide growth factors , including nerve growth factor ( NGF ) and its cognate receptor TrkA have been shown to be strongly expressed in atherosclerotic lesions , the present study was undertaken to evaluate in vitro , the activity of NGF with regard to apoptosis of confluent cultures of human aortic SMCs . ^^^ The pro apoptotic activity of NGF was blocked in a dose dependent manner by K 252a , an inhibitor of TrkA tyrosine phosphorylation , suggesting that a NGF / TrkA signal transduction pathway could activate apoptotic cell death programs in human SMCs . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
While the central role played by TrkA in nerve growth factor ( NGF ) signalling has been established by dissecting its signal transduction pathways , insight into the mechanism of action of p75LNR , the low affinity neurotrophin receptor , has only recently been achieved . ^^^ The relative contribution of p75LNR and TrkA to the constitution of high affinity receptors for NGF and , similarly , with TrkB an TrkC to the formation of those for other neurotrophins , is presently under debate . ^^^ In the present work , we have ectopically coexpressed p75LNR and TrkA in Sf 9 insect cells by using baculovirus vectors , and show a direct association between the two NGF receptors . ^^^ Finally , we demonstrate that NGF becomes endocytosed in TrkA expressing cells but not in p75LNR expressing cells , and that such function can be modulated by the presence of the intracellular domain of p75LNR receptor . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We found that TrkA , the receptor tyrosine kinase that mediates many NGF responses , is expressed primarily by neurons in these cultures , suggesting a presynaptic mechanism for the effects of NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Steady state expression of transcripts for neurofilament ( NF ) proteins ( NF L , NF H ) and the high affinity NGF receptor , trkA was decreased by diabetes in the contralateral ganglia to the crush ( all P < 0 . 05 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Here we present evidence that the mRNAs for NGF , trkB and BDNF but not trkA are localised in the dendrites of rat neurons , thus implying that neurotrophins and their receptors can be synthesised at locations close to their sites of function , with particular regard to the dendritic synapses . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Phenotypic analyses of mice lacking neurotrophin receptors , TrkA , B and C , confirm that TrkA is the functional receptor for NGF , TrkB acts as the primary receptor for BDNF and NT 4 , and NT 3 signals primarily through TrkC . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The present data give evidence for the expression of TrkA , the so called high affinity NGF receptor , and of p75NTR , the so called low affinity NGF receptor . ^^^ Exposure of OLs to NGF induces an autophosphorylation of TrkA via its intrinsic tyrosine kinase . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA expression levels of sympathetic neurons correlate with NGF dependent survival during development and after treatment with retinoic acid . ^^^ We have investigated the expression of the signal transducing NGF receptor trkA on mRNA and protein level during development of chick sympathetic neurons obtained from lumbosacral , paravertebral chain ganglia between embryonic days ( E ) 6 . 5 and 10 . ^^^ To define the correlation between trkA expression and NGF mediated survival in more detail , trkA expression was adjusted to different levels by treatment with increasing concentrations of retinoic acid . ^^^ We observed that small changes of trkA mRNA expression levels , below one order of magnitude , are decisive for the ability of immature sympathetic neurons to survive in the presence of NGF . ^^^ These data provide evidence that sympathetic neurons upregulate the NGF receptor trkA and in this way acquire NGF dependency . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Furthermore , specific inhibitors for trkA and PDGF RTK activities abrogate sodium channel inhibition in response to NGF and PDGF , respectively , showing that the intrinsic RTK activity of these receptors is necessary for sodium channel inhibition . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Aged ( 20 22 months old ) and young ( 3 months old ) Sprague Dawley rats were treated with GM 1 ganglioside , 30 mg / kg i . p . for 30 days , and the content of nerve growth factor ( NGF ) and the high affinity tyrosine receptor kinase ( Trk ) examined . ^^^ GM 1 treatment partially restored NGF and NGF mRNA in frontal cortex and hippocampus in the aged brain , but treatment had no effect on Trk protein . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The fact that increased nerve growth factor ( NGF ) protein levels were found throughout brains of Alzheimer ' s disease patients led us to investigate neurotrophin synthesis in a human microglial cell line showing typical properties of human microglial cells , including expression of neurotrophins such as NGF , as well as the NGF receptor trkA and the low affinity neurotrophin receptor p 75 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These receptors are trkA , which binds NGF ; trkB , which binds both BDNF and NT 4 / 5 ; and trkC , which binds NT 3 . ^^^ The results show that smooth muscle stromal cells expressed NGF , BDNF and trkC , whereas both epithelial cell lines expressed trkA , trkB and trkC to various degrees . ^^^ This suggests that the stromal cell derived NGF and BDNF may interact via paracrine mechanisms with trkA and trkB receptors , respectively , on the adjacent epithelial cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In contrast , in the triple mutant D72A / S73A / K74A , the simultaneous replacement of Asp 72 and Lys 74 with alanine had a compensatory effect such that binding to both p 75 and TrkA was comparable to that of wild type NGF , despite the deficits seen in the individual replacements . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To address the potential relationship between p 75 ( NTR ) signaling and OL injury , we assayed adult human OLs cultured under several different conditions for p 75 ( NTR ) and tyrosine kinase receptor trkA expression , for NGF mediated apoptosis , and for NGF mediated jun kinase ( JNK ) or nuclear factor ( NF ) kappaB activation . ^^^ These findings contrast with the recent report of NGF mediated apoptosis in the OLs of neonatal rats matured in vitro , which express p 75 ( NTR ) but not trkA ( ) , and suggest that , at least in humans , p 75 ( NTR ) signaling may mediate responses other than apoptosis of OLs . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
When sympathetic neuron survival is maintained with low quantities of NGF or KCl , the neurotrophin brain derived neurotrophic factor ( BDNF ) , which does not activate Trk receptors on sympathetic neurons , causes neuronal apoptosis and increased phosphorylation of c jun . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Recently it has become apparent that sympathetic neurons of rat superior cervical ganglia ( SCG ) acquire sensitivity to neurotrophin 3 ( NT 3 ) before they become dependent on the target derived nerve growth factor ( NGF ) for their survival by sequential induction of TrkC and TrkA . ^^^ BMP 2 treatment , on the other hand , promoted the effect of RA on the suppressions of trkA mRNA levels and the NGF dependent survival of the SCG neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We show that the Akt / PKB pathway is essential for NGF stimulated TrkA survival signalling in the case of U . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Mobility of TrkA is regulated by phosphorylation and interactions with the low affinity NGF receptor . ^^^ The nerve growth factor ( NGF ) receptor is a complex of two proteins , gp 75 and the tyrosine kinase TrkA . ^^^ Addition of NGF to the medium approximately halved the mobile fraction for TrkA in both the absence and presence of gp 75 . ^^^ Therefore , two mechanisms lead to NGF induced immobilization of TrkA the first resulting from autophosphorylation of TrkA and the second occurring through TrkA ' s association with gp75 . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The neurotrophic activity of APP was independent of the TrkA NGF receptor because neither phospholipase C gamma 1 nor TrkA exhibited tyrosine phosphorylations with APP treatment . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We quantitated mRNA levels of neurotrophins ( NGF , BDNF , NT 3 , NT 4 / 5 ) and their receptors ( trkA , trkB , trkC , p 75 ) in AD postmortem parietal cortex ( n = 16 ) and cerebellum ( n = 11 ) . ^^^ This finding suggests that a reduced expression of the trkA receptor may contribute to impaired NGF trkA signalling and a reduced transport of NGF in cholinergic neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Neurotrophin expression was not unique to adult tissues since pancreatic cells transiently expressed p 75 , the NGF receptor Trk A , and NGF during development . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We studied the expression of neurotrophin receptors ( trk A , trk B , trk C ) and their responsiveness to neurotrophins ( NGF , BDNF , NT 3 ) in 25 human neuroblastomas using a primary culture system . ^^^ The tumours in early stages and stage 4s responded to both NGF and NT 3 , but not to BDNF , by surviving and differentiating terminally and the responsiveness was correlated with high levels of trk A , especially the neuronal isoform . ^^^ Interestingly , a stage 4 tumour with MYCN amplification which expressed high level of neuronal trk A was dependent on nerve growth factor ( NGF ) for both survival and differentiation in primary culture . ^^^ The results suggest that the NGF / trk A signalling may be the main regulatory pathway for differentiation and survival of neuroblastoma in vivo and that trk A overexpression may overcome aggressiveness , even of the tumour with MYCN amplification . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In neuroblastoma tumours , the expression of high levels of trk A mRNA , which encodes the high affinity nerve growth factor ( NGF ) receptor , is associated with good prognosis . ^^^ Treatment of the 15N trk A clones with NGF inhibited proliferation ( 80 90 % decrease ) , while treatment of the 15N trk B clone with BDNF had no effect ( < 10 % decrease ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Monoclonal antibody to human Trk A : diagnostic and therapeutic potential in neuroblastoma . 5C3 is a murine IgG 1 antibody specific for the nerve growth factor ( NGF ) docking site of the human p 140 trk A receptor , with no cross reactivity with human trk B . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Levels of trkA and BDNF mRNA , but not NGF mRNA , fluctuate across the estrous cycle and increase in response to acute hormone replacement . ^^^ In the present study , quantitative in situ hybridization techniques were used to determine whether the levels of trkA mRNA in the basal forebrain , and nerve growth factor ( NGF ) mRNA and brain derived neurotrophic factor ( BDNF ) mRNA in the hippocampus , are significantly affected by physiological changes in circulating gonadal steroids . ^^^ No significant changes in trkA mRNA were detected in the nucleus basalis magnocellularis , and no significant changes in NGF mRNA were detected in the hippocampus . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF treatment of PC 12 or TrkA transfected Chinese hamster ovary ( CHO ) cells results in a rapid , transient increase in the extracellular acidification rate as measured by the Cytosensor ; in both cell types , p75LNTR enhances this response . p75LNTR affects both the magnitude of and the duration of the extracellular acidification response to NGF . ^^^ Moreover , it is not merely the presence of p75LNTR , but also the ratio of p75LNTR : TrkA which determines cellular responsiveness to NGF . ^^^ In transiently transfected CHO cells , a 5 : 1 ratio of p75LNTR : trkA cDNAs produced the greatest change in NGF induced acid secretion . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In contrast to medulloblastomas , TrkA and NGF co distributed in other pediatric brain tumors , and both Trk receptors and their neurotrophins co distributed with GFAP positive tumor cells in 13 ( 42 % ) of the non PNET pediatric brain tumors . ^^^ TrkA , TrkB , and TrkC were observed in 5 ( 25 % ) , 8 ( 40 % ) , and 17 ( 85 % ) , respectively , of these medulloblastomas while NGF , BDNF , and NT 3 were observed in 6 ( 30 % ) , 8 ( 40 % ) , and 3 ( 15 % ) , respectively , and antibodies to neurofilament ( NF ) and glial fibrillary acidic proteins ( GFAP ) stained 16 ( 80 % ) and 11 ( 55 % ) , respectively . ^^^ TrkA and NGF were not observed in the same biopsy samples , while TrkB and BDNF were co distributed in 6 of the cases , all of which expressed NF proteins . ^^^ The absence of medulloblastomas that contain NGF and TrkA is consistent with in vitro data demonstrating that NGF mediated TrkA signaling induces apoptosis . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
As determined by transient expression , two NGF response elements ( REs ) were required for transcription induced by NGF in SH SY5Y cells with stable expression of an exogenous NGF receptor TRK A gene ( SH SY5Y / trk ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Expression of mRNAs for neurotrophins ( NGF , BDNF , and NT 3 ) and their receptors ( p75NGFR , trk , trkB , and trkC ) in human peripheral neuropathies . ^^^ The steady state mRNA levels of NGF , BDNF and NT 3 , and the mRNA levels of their receptors p75NGFR , trk , trkB , and trkC were examined in various human peripheral neuropathies , to determine the correlation with myelinated fiber pathology and T cell and macrophage invasions in the diseased nerves . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The competition profiles for the transport of NT 3 and NGF are consistent with the presence of TrkA and TrkC and the absence of TrkB in the nodose ganglion , whereas the profile for NT 4 suggests a p 75 receptor mediated transport mechanism . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Although both NGF receptors are expressed constitutively by LA N 2 cells , CNTF has a marked stimulatory effect on trkA mRNA and protein . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The upregulation of mRNA levels for NGF , two BDNF variants with exons 1 and 2 , low affinity neurotrophin receptor , and high affinity receptors , TrkA ( for NGF ) and TrkB ( for BDNF ) , was observed in response to the treatment with serum and phorbol ester following the serum starvation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Next , we investigated the tyrosine phosphorylation of NGF receptor TrkA and the EGF receptor ( EGFR ) as well as mitogen activated protein kinase ( MAPK ) , which is a key protein in the intracellular signal transduction pathway . ^^^ MS 430 also prolonged the NGF induced phosphorylation of MAPK , but the phosphorylation of TrkA induced by NGF was not affected by MS 430 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The neurotrophin family of growth factors , which includes Nerve Growth Factor ( NGF ) , Brain Derived Neurotrophic Factor ( BDNF ) , Neurotrophin 3 ( NT 3 ) and Neurotrophin 4 / 5 ( NT4 / 5 ) bind and activate specific tyrosine kinase ( Trk ) receptors to promote cell survival and growth of different cell populations . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In addition , APPs synergistically potentiated the tyrosine phosphorylation of trkA due to NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In addition , our results show that MKP 1 mRNA is induced after NGF stimulation of fibroblasts expressing the NGF receptor TrkA , suggesting that MKP 1 is upregulated after activation of the TrkA receptor . ^^^ These data show that the MKP 1 gene is regulated in a tissue and temporal specific fashion with strong expression in the developing peripheral ganglia , and suggest that the activation of MKP 1 mRNA expression by NGF is a ubiquitously induced response to TrkA activation , independent of the cellular origin or type on which the TrkA receptor is active . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) acts as an anti mitogenic factor in C 6 2B glioma cells stably expressing TrkA ( C6trk+ ) . ^^^ Analysis of this tumor showed that expression of TrkA was retained , but the synthesis of NGF was abolished . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Recombinant zNT 7 was able to bind to the human p 75 neurotrophin receptor and to induce tyrosine phosphorylation of the rat TrkA receptor tyrosine kinase , albeit less efficiently than rat NGF . zNT 7 did not interact with rat TrkB or TrkC , indicating a similar receptor specificity as NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These neurons also preferentially express the high affinity receptor for nerve growth factor ( NGF ) , TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The dorsal root ganglia ( DRGs ) were sampled at various times throughout the experiment and processed for in situ hybridization to examine mRNA expression of the NGF receptors ( p 75 and trkA ) and GAP 43 . ^^^ As well , expression of mRNAs for the neurotrophins NGF , BDNF , and NT 3 was examined . p 75 , trkA , and GAP 43 mRNAs were upregulated in DRGs from the NGF treated , but not the control animals . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Our results show that NGF induces a rapid increase of cell surface LRP expression in a central nervous system derived neuronal cell line , GT 1 1 Trk , which was seen within 10 min and reached a maximum at about 1 h of NGF treatment . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To further support this hypothesis , we have studied the expression of Trk A , the high affinity receptor for NGF , in vivo during the embryonic and fetal development of the rat pancreas . ^^^ The expression of Trk A and its ligand NGF in the pancreas during embryonic and fetal life suggests that NGF and its receptor could play an important role in the development of the pancreas . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Its biological functions were partly due to the increasing endogeneous NGF and its high affinity receptor , trk A productions . ^^^ NGF , trk A mRNA levels and Fas protein expressions were increased , whereas bcl 2 mRNA level was decreased . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Over expression of NGF in skin causes formation of novel sympathetic projections to trkA positive sensory neurons . ^^^ To test this , double label immunohistochemistry for the NGF receptor ( trkA ) and sympathetic baskets was performed . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
All specimens were histologically stained , and immunohistochemistry was performed to identify the NGF high affinity receptor ( TrkA ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) , neurotrophin 3 , neurotrophin 4 , and brain derived neurotrophin exert their survival effect by binding to two transmembrane receptor types : trk receptors , which exhibit binding specificity , and the p75NTR receptor , which binds all neurotrophins . ^^^ Previous studies of trk expression in trigeminal ganglia of adult NGF transgenics showed that the percentage of trkA neurons doubled and their number increased fivefold . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In addition , we hypothesize that the decreases in trkA mRNA detected both in the MS as a function of aging , and in the MS and NBM in response to ovariectomy , reflect decreases in the production of high affinity nerve growth factor ( NGF ) receptors , and a decrease in the responsiveness of the cholinergic neurons to endogenous NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These latter functional effects mimicked influences on NGF mediated neurite growth in other trkA positive cells as reported previously . ^^^ NGF dependent trkA phosphorylation was significantly enhanced by the presence of the peptide , whereas high affinity binding of 125I NGF , both NGF receptors mRNA and protein expression , and trkA dimer / monomer ratios were not influenced . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
However , these neurons can be rendered NGF responsive by transducing them with the high affinity receptor for NGF , TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These bidirectional effects of neurotrophins appear to be mediated by the neurotrophin specific Trk receptors on the growth cones since most growth cones are immunopositive for TrkA and TrkB , the NGF and BDNF receptors , respectively , and k252a , a selective inhibitor of Trk mediated responses to neurotrophins , diminishes collapsin 1 induced growth cone collapse . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Rabbit polyclonal antibodies against neurotrophins ( nerve growth factor NGF , brain derived neurotrophic factor BDNF and neurotrophin 3 NT 3 ) and against specific epitopes of TrkA , TrkB and TrkC proteins were used . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
High doses of bryostatin blocked NGF induced neurite outgrowth without altering Y 490 TrK A phosphorylation or an alteration in pp44 / 42 mitogen activated protein kinase . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Since none of the trk high affinity neurotrophin receptors could be demonstrated in C2C12 cells , we conclude that NGF mediates its nonneurotrophic effect via its low affinity receptor in an autocrine fashion . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The in vivo targeting efficacy of small molecule analogs of nerve growth factor ( NGF ) that bind the NGF receptor p 140 TrkA was evaluated and compared with that of a high affinity anti TrkA monoclonal antibody ( Mab 5C3 ) . ^^^ Tumors that do not express TrkA were not targeted , demonstrating the specificity of NGF mimics in vivo . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF stimulated changes in morphology and function are mediated by high affinity Trk A receptors in other mammalian cells . ^^^ Trk A receptors are present in beta cells and steady state levels of Trk A mRNA are modulated by NGF and dibutyryl cAMP . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This review will discuss recent studies and examine the role members of the nerve growth factor family ( NGF , BDNF and NT 3 ) and trk receptors as well as additional growth factors ( GDNF , TGF alpha and IGF 1 ) may play in neurodegenerative disorders of the human brain . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Mystacial pads were analyzed from newborn to 4 week old mice that had homozygous functional deletions of the genes for NGF , brain derived neurotrophic factor ( BDNF ) , neurotrophin 3 ( NT 3 ) , neurotrophin 4 ( NT 4 ) , tyrosine kinase ( trk ) A , trkB , trkC , or p 75 . ^^^ The cumulative results indicated that NGF / trkA signaling plays a major role in the outgrowth and proliferation of sensory axons , whereas NT 3 / trkA signaling plays a major role in the formation of sensory endings . ^^^ Another set of sensory innervation that only coexpressed CGRP and SP was solely dependent upon NGF and trkA . ^^^ In contrast to sensory innervation , sympathetic innervation to the necks of intervibrissal hair follicles depends upon NGF / trkA signaling interacting with p 75 for both the axon outgrowth and ending formation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immunoblotting experiments revealed that both the two cancer cell lines and the NBEC express high affinity ( p 140 ( trk ) ) and low affinity ( p 75 ) NGF receptors . ^^^ Inhibition of the NGF growth promoting effect by the drugs K 252a and PD 98059 indicated that activation of Trk tyrosine kinase activity and the mitogen activated protein kinase cascade are necessary to obtain the mitogenic effect . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We expressed the high affinity nerve growth factor receptor TrkA in Chinese hamster ovary ( CHO ) fibroblasts to study nerve growth factor ( NGF ) trafficking and processing events following receptor mediated ligand internalization in a nonneuronal and p 75 minus cell line . ^^^ These stable clonal cell lines express approximately 2 . 5 10 10 ( 5 ) TrkA receptors and bind 125I NGF with high affinity ( Kd = 4 10 10 ( 10 ) M ) . ^^^ The TrkA receptors are autophosphorylated on tyrosine residues upon NGF stimulation and are capable of tyrosine phosphorylating downstream signaling molecules . ^^^ The t1 / 2 of 125I NGF internalization is 5 min , and the probability of an occupied TrkA receptor internalizing within 1 min at 37 C is 9 . 8 % . ^^^ Thirty minutes following ligand endocytosis , endocytosed 125I NGF is delivered back to the cell surface and released by the cell ( retroendocytosis ) , possibly by remaining associated with recycling TrkA receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF can bind independently to two different receptors , the trkA tyrosine kinase receptor and the p 75 neurotrophin receptor , which are involved in many different signaling events . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These results demonstrate that in vivo TrkA tyrosine kinase activity , actin filaments and dynein are involved in the retrograde transport of NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The pheochromocytoma PC 12 cell line was used as a model system to characterize the role of the p 75 neurotrophin receptor ( p75NTR ) and tyrosine kinase ( Trk ) A nerve growth factor ( NGF ) receptors on amyloid precursor protein ( APP ) expression and processing . ^^^ NGF increased in a dose dependent fashion neurite outgrowth , APP mRNA expression , and APP secretion with maximal effects at concentrations known to saturate TrkA receptor binding . ^^^ These findings demonstrate that in PC 12 cells expressing p75NTR and TrkA receptors , binding of NGF to the p75NTR is required to mediate NGF effects on cell morphology and APP metabolism . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
BACKGROUND : TrkA , the high affinity , tyrosine kinase receptor for nerve growth factor ( NGF ) has been implicated as an oncogene in several neoplasms . ^^^ In prostate cancer , inhibitors of the NGF / TrkA signal pathway results in tumor growth inhibition . ^^^ However , the absence of mutations in otherwise genetically unstable prostate tumor DNA suggests that intact NGF / TrkA pathways may be important in prostate cancer development . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In contrast to the effect of NGF and ACPD on glutamate release in control rats , the combination of these agents had no effect on release in synaptosomes prepared from GH rats , which might be explained by the marked decrease in trk receptors in dentate gyrus of GH rats . ^^^ It was concluded that the impaired ability of GH rats to sustain LTP is associated with a reduction in NGF concentration , a reduction in stimulated release of NGF and a decrease in trk receptors in dentate gyrus . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The precise signaling pathways leading to each of the cellular responses mediated by receptor tyrosine kinases are still unknown , although it has been proposed that sustained activation of the MAPK pathway by receptor tyrosine kinases such as the nerve growth factor ( NGF ) receptor TrkA is sufficient to induce differentiation in PC 12 cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Human skin , including nerves and sensory corpuscles , displays immunoreactivity ( IR ) for low ( p 75 ) and high affinity ( TrkA like ) receptors for nerve growth factor ( NGF ) , the best characterized member of the family of neurotrophins . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Here we report that meningeal cells in the pia mater express immunoreactivity and mRNA for both known NGF receptors , the low affinity receptor p 75 and the tyrosine kinase receptor trkA . ^^^ NGF induces rapid tyrosine phosphorylation of trkA in meningeal cells in vitro . ^^^ NGF does not stimulate proliferation of primary meningeal cells but induces process outgrowth . p 75 and trkA immunoreactive meningeal cells with long processes , resembling NGF treated cells in vitro , are abundant in the scar tissue that forms at spinal cord lesions in rat and cat . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Furthermore , we analyzed the expression of specific growth factors and growth factor receptors in the ST14A cells , and found that nerve growth factor ( NGF ) and Trk receptors are most commonly expressed . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Neurotrophins act , in large part , through Trk receptor tyrosine kinases : nerve growth factor ( NGF ) via TrkA , brain derived neurotrophic factor ( BDNF ) and neurotrophin 4 / 5 ( NT 4 / 5 ) via TrkB , and neurotrophin 3 ( NT 3 ) via TrkC . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
No change of trkA receptor immunostaining was seen in DRGs of diabetic rats ; however , a reduction of trkA immunoreactivity of DRG neurons was noted after long term NGF treatment of healthy controls . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These results suggest that NGF induced increase in Ca2+ channel current in adult sympathetic neurons results , at least in part , from new channel synthesis after Trk activation of Ras and mitogen activated protein kinase by a mechanism that is independent of extracellular Ca2+ . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
However , the role of NGF in relation to its high affinity trkA receptor in the cortical neurons has not been well discussed . ^^^ Brain sections at the level of striatum were immunostained against NGF , trkA , glial fibrillary acidic protein ( GFAP ) , and stress protein HSP 70 . ^^^ CONCLUSIONS : Our study demonstrated a temporal profile of NGF and trkA in the ischemic cortex and NGF expression by reactive astrocytes . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Expression of the nerve growth factor ( NGF ) receptors TrkA and p 75 ( NTR ) was found to vary at the surface of PC 12 cells in a cell cycle phase specific manner . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF failed to suppress the increase in ROS in the PC 12 variant nnr 5 , which lacks p 140 ( trk ) receptors . ^^^ The suppression of the increase in ROS by NGF was restored in nnr 5 cells stably expressing p 140 ( trk ) ( nnr 5 trk ) , but NGF failed to prevent the increase in ROS in nnr cells expressing mutant p 140 ( trk ) receptors that lack binding sites for Shc and phospholipase Cgamma . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In contrast , human bone marrow cells consistently expressed mRNA for trkB ( the BDNF and NT 4 receptor ) and displayed variable expression of mRNA coding for trkA ( the tyrosine kinase NGF receptor ) and LNGFR ( the low affinity NGF receptor ) , whereas mRNA for trkC ( the NT 3 receptor ) was not expressed . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To assess the importance of adaptor proteins and Ras in NGF control of phosphoinositide 3 OH kinase ( PI 3 kinase ) , specific receptor mutations in Trk have been employed . ^^^ The TrkA receptor protein tyrosine kinase is involved in signalling PC 12 cell differentiation and cessation of cell division in response to nerve growth factor ( NGF ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Because NO affects both neural plasticity and degeneration , and trk receptors can mediate signaling within minutes , we hypothesized that NGF might rapidly modulate NO production . ^^^ Most NGF signaling is thought to occur after internalization and retrograde transport of trkA receptor and be mediated through the nucleus . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Using the mice which had received unilateral olfactory bulbectomy and in which antibodies to NGF had been continuously infused with into the contralateral olfactory blub , three kinds of analysis were performed : histological analysis of the olfactory epithelium by HE staining , immunohistochemical analysis of the olfactory epithelium using polyclonal antibodies to trk which forms the NGF receptor , and olfactory mediated behavioral analysis with cycloheximide . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Our previous studies have shown that cholera toxin B subunit , which specifically binds to the cell surface ganglioside GM 1 , and GM 1 itself can enhance the action of nerve growth factor ( NGF ) in responsive cells by enhancing the NGF induced autophosphorylation of the high affinity NGF receptor , Trk . ^^^ Moreover , D PDMP clearly inhibited NGF induced autophosphorylation of Trk and prevented the activation of phosphatidylinositol 3 kinase and mitogen activated protein kinase , downstream targets of Trk initiated intracellular protein kinase cascades . ^^^ The present results and our previous observations clearly demonstrate that Trk requires endogenous gangliosides , especially GM 1 , for its normal function in mediating the neurotrophic activity of NGF at least in PC 12 cells . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF induced tyrosine phosphorylation of phospholipase Cgamma , TrkA , and Shc was unaltered in the Shb overexpressing cells , whereas that of Shb was greatly enhanced in these cells compared with control PC 12 neo cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have characterized some of the nerve growth factor ( NGF ) stimulated receptor tyrosine kinase ( TrkA ) signalling cascades in adult rat primary dorsal root ganglia ( DRG ) neuronal cultures and compared the pathways with those found in PC 12 cells . ^^^ TrkA receptors were phosphorylated on tyrosine residues in response to NGF in DRG neuronal cultures . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The role of TrkA and p75NTR receptors was investigated in NGF induced potentiation of glutamate release . ^^^ Activation of TrkA in isolation by RTA IgG , an antibody that specifically activates TrkA , was less effective than activation of both receptors by NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Mutant mice in which TrkA , the high affinity receptor for nerve growth factor ( NGF ) , has been inactivated lack nociceptive neurones in sensory ganglia and do not respond to noxious stimuli . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Equilibrium binding of 125I nerve growth factor ( 125I NGF ) to cells coexpressing the tyrosine kinase receptor A ( TrkA ) and common neurotrophin receptor ( p75NTR ) , cells coexpressing both receptors where p75NTR is occupied , and cells expressing only p75NTR , revealed reciprocal modulation of receptor affinity states . ^^^ These data are consistent with receptor allosterism , and prompted a search for TrkA / p75NTR complexes in the absence of NGF . ^^^ The heteroreceptor complex of TrkA and p75NTR alters conformation and / or dissociates in the presence of NGF , as indicated by the ability of low concentrations of NGF to prevent heteroreceptor crosslinking . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Two types of receptors mediate the actions of these polypeptides : the Trk family of tyrosine kinase receptors and the so called p 75 low affinity NGF receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
About 60 % and 35 % of the lumbar DRG neurons expressed c ret and trkA , proto oncogenes of the functional receptors for GDNF and NGF , respectively . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Furthermore , the high affinity NGF receptor ( TrkA ) was found at both the transcriptional and protein levels , while expression of the low affinity NGF receptor was detectable at the mRNA level only . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Recent experiments with NGF responsive cells revealed a specific role for the high affinity NGF receptor , TrkA , in the increases in secretory APP processing and a role for the low affinity neurotrophin receptor , p75NTR , in the transcriptional regulation of APP . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The reverse transcription polymerase chain reaction , immunocytochemical staining , and Western blotting revealed that cultured microglia express Trk A , B , and C , and low affinity NGF receptor , LNGFRp 75 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In contrast , expression of trk A , the high affinity receptor for nerve growth factor ( NGF ) , was down regulated by LPS . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Our results on tyrosine kinase ( Trk ) coexpression , suggest that NGF may cooperate with other factors in the cholinergic phenotype differentiation and maintenance after the second postnatal week . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA antagonists decrease NGF induced ChAT activity in vitro and modulate cholinergic synaptic number in vivo . ^^^ By using a synthetic TrkA antagonist we demonstrated that endogenously produced NGF is involved in the continual re modeling of cholinergic neuronal connections during adulthood , acting through TrkA receptors . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We also investigated the novel effect of nerve growth factor ( NGF ) treatment on the levels of mRNA and protein of the NGF receptors , trkA and p75NTR , in normal and diabetic rats . ^^^ Treatment with systemic NGF reversed the diabetes induced deficit in p75NTR transcripts and protein within the DRG and left expression levels of trkA unchanged . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Radiolabeled NGF was transported in a receptor mediated fashion from the teeth to a subset of neurons in the trigeminal ganglion within 15 h , indicating that these neurons possess NGF receptors ( trk A and / or p75NTR ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
DEX elicited an increase in NGF mRNA and protein levels in the cerebral cortex and hippocampus as well as specific NGF responses , such as TrkA tyrosine phosphorylation in the septum , choline acetyltransferase ( ChAT ) and p 75 neurotrophin receptor ( p75NTR ) immunoreactivity , and a relative number of cholinergic neurons in the medial septum . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF binds to tropomyosin receptor kinase A ( TrkA ) and to 75 kDa NGF receptor ( p75NTR ) . ^^^ TrkA is responsible for differentiation and survival , but p75NTR , a member of the death receptor family , seems to mediate the apoptotic effect of NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
As a first step to learning about the possible functional role of NGF in the astroglial response during neurodegeneration , we have analyzed the expression of the functional receptor for NGF , TrkA , in human neurodegenerative diseases which are accompanied by reactive astrocytosis , as well as in human astrocytomas . ^^^ The presence of TrkA receptors in reactive astrocytes from different human neurodegenerative diseases and experimentally induced models in rats , and in neoplastic astrocytes suggests that NGF may participate in the astroglial response to different types of injury and neoplastic proliferation . ^^^ Since astroglial cells are capable of producing NGF , it is plausible that this neurotrophin may function as an autocrine or paracrine factor in TrkA expressing reactive and neoplastic glial cells . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Since NGF can act through two receptors types , the high affinity tyrosine kinase A ( trkA ) receptor and the low affinity p 75 receptor , we used transgenic mice lacking p 75 to analyse the relative importance of these receptors . ^^^ This means that NGF induced hyperalgesia can occur in the absence of the p 75 receptor and suggests that the trkA receptor is sufficient to mediate the acute noxious action of NGF . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Functional nerve growth factor ( NGF ) responsiveness was investigated in human neuroblastoma ( NB ) cell lines in vitro and retinoic acid ( RA ) was found to transcriptionally enhance expression of the trkA , but not the trkB gene in GOTO cells , while the reverse was found in HTLA 230 NB cells . ^^^ Transcriptional activation of the trkA gene increased total trkA protein and surface bound receptor , which was tyrosine phosphorylated upon NGF stimulation inducing immediate early response gene transcription ( i . e . c fos , Egr 1 ) . ^^^ Rapid down regulation of the receptor protein occurred upon NGF stimulation , despite the presence of high levels of trkA mRNA , due to an increased rate of receptor degradation . ^^^ Transient DNA synthesis and cell proliferation upon NGF treatment occurred in GOTO cells with elevated trkA expression . ^^^ In contrast , NGF induced neuronal differentiation in HTLA 230 cells expressing the endogenous trkA receptor gene , despite the lack of p 75 expression . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) initiates its biological effects by promoting the dimerization and activation of the tyrosine kinase receptor TrkA . ^^^ The requirements for NGF signaling through the TrkA receptor have been defined extensively from studies in immortalized cells , involving transfection of NIH 3T3 , COS , and PC 12 cells . ^^^ In contrast with previous observations in a PC 12 background , a mutation in the SHC Y 490 binding site in TrkA resulted in a loss of NGF dependent process formation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The NGF target is localized at a postsynaptic site and involves a new TrkA like receptor . ^^^ The squid receptor crossreacts with antibodies generated against mammalian TrkA , is tyrosine phosphorylated in response to NGF stimulation , and is blocked by specific pharmacological inhibitors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To stimulate TrkA and / or p75NTR signaling in PC 12 cells , we used NGF , brain derived neurotrophic factor ( BDNF ) , and NGF in the presence of an excess of BDNF or the monoclonal antibody 192IgG , to block p75NTR binding to NGF . ^^^ These findings suggest that in cells expressing p75NTR and TrkA receptors , binding of NGF to the p75NTR is required to mediate NGF effects on APP secretion . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Naturally occurring sympathetic neuron death is the result of two apoptotic signaling events : one normally suppressed by NGF / TrkA survival signals , and a second activated by the p 75 neurotrophin receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have studied the high affinity NGF receptor TrkA , during the regeneration of the tench ( Tinca tinca L . ) optic nerve , using immunocytochemical techniques . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) is a neurotrophin that induces neuritogenic and trophic signals by binding to TrkA and / or p 75 receptors . ^^^ NGF . mAb complexes do not bind p 75 effectively but bind TrkA with high affinity . ^^^ NGF . mAb induced activation of TrkA , Shc , and MAPK is transient compared with NGF induced activation ; yet NGF and NGF . mAb afford identical trophic responses . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Northern blot analysis further demonstrated different patterns of induction of c myc , vgf and trkA mRNA transcription in PC 12 pheochromocytoma cells treated with NGF and NLP , respectively . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This inhibition may be due to a direct interaction of caveolin with Trk A , because Trk A co immunoprecipitated with caveolin from Cav Trk A PC 12 cells , and a glutathione S transferase caveolin fusion protein bound to Trk A and inhibited NGF induced autophosphorylation in vitro . ^^^ Furthermore , the in vivo kinetics of the inhibition of Trk A tyrosine kinase activity by caveolin expression correlated with an increased ability of NGF to induce sphingomyelin hydrolysis through p 75 ( NTR ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Like suramin and NGF , PPS induced neurite outgrowth from the PC 12 cell line which correlated with tyrosine phosphorylation of the high affinity NGF receptor ( TrkA / gpl40 ) and ERK 1 / MAP kinase . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The percentage of neuronal profiles surrounded by TH IR baskets following sciatic transection was unaffected following peripheral application of the NGF sequestering antibody , trkA IgG ( 1 mg / ml , 14 days ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The phosphorylation of Vav and activation of Ras triggered by NGF is mediated through Trk tyrosine kinase , whereas signaling through the BCR uses a different tyrosine kinase . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have tested the localization and the molecular nature of the NGF receptor ( s ) responsible for this effect by activating cortical trkA receptors in monocularly deprived rats by cortical infusion of a specific agonist of NGF on trkA , the bivalent antirat trkA IgG ( RTA IgG ) . ^^^ These results suggest that NGF action in visual cortical plasticity is mediated by cortical TrkA receptors with p75NTR exerting a facilitatory role . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Within this population , VR 1 mRNA is detected at widely varying levels in both the NGF receptor ( trkA ) positive , peptide producing cells that elicit neurogenic inflammation and the functionally less characterized glial cell line derived neurotrophic factor responsive cells that bind lectin Griffonia simplicifolia isolectin B 4 ( IB 4 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
DRG neurons cultured from rats with high antibody titers to NGF , which do not bind the isolectin IB 4 ( IB 4 ( ) ) but do express TrkA , were studied with whole cell patch clamp and in situ hybridization . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The present study examined the effect of long term ( 90 days ) daily injections of an estrogen preparation , Premarin ( Wyeth Ayerst , Radnor , PA ) , to ovariectomized adult rats on lumbar DRG high affinity NGF receptor , trkA , mRNA levels , and on beta preprotachykinin ( beta PPT ) mRNA levels , which have been shown to be regulated by NGF . ^^^ Moreover , as would be expected if beta PPT gene expression is regulated by NGF through the trkA receptor , long term estrogen treatment decreased DRG neuronal beta PPT mRNA levels by about 30 % . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Moreover , Trk A , the nerve growth factor ( NGF ) high affinity receptor , is expressed in vivo in mature rat islets and early during development in the pancreatic ductal network that represents the source of putative stem cells . ^^^ Moreover , on treatment with NGF , Trk A is phosphorylated and early responsive genes such as NGFI A , c fos and c jun are induced . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF is increased in inflamed tissues , and acts via its high affinity receptor trk A on nociceptor fibres to produce hyperalgesia . ^^^ Anti NGF or anti trk A agents may represent novel analgesics in this condition . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We examined contributions of the NGF receptors trk and p 75 and of the major NGF signaling pathways to proliferation versus neurite outgrowth . ^^^ The type of initial NGF response does not correlate with intensity of immunoreactivity for trk or p 75 . ^^^ Mitogenic cooperativity between receptors at low NGF concentrations is suggested by inhibitory effects of p 75 blocking antibodies , but responses to trk agonist antibody indicate that trk activation alone can induce proliferation . ^^^ Trk agonist antibody , which is as mitogenic as NGF but less neuritogenic , causes equally prolonged but less intense ERK phosphorylation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF did not elicit tyrosine phosphorylation of Trks whereas BDNF induced Trk tyrosine phosphorylation within 10 min , followed by time dependent decrease . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Further studies using mutant trk receptors will help to define the signal transduction pathways mediating NGF induced smooth muscle cell migration . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Each neurotrophin has its preferred receptor , i . e . trkA for NGF , and trkC for NT 3 . ^^^ Some of the small sensory neurons express trkA and are NGF dependent . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Consistent with this model , FRS 2 binds Grb 2 , Crk , the SH 2 domain containing tyrosine phosphatase SH PTP 2 , the cyclin dependent kinase substrate p 13 ( suc 1 ) , and the Src homology 3 ( SH 3 ) domain of Src , providing a functional link between TrkA , cell cycle , and multiple NGF signaling effectors . ^^^ Importantly , overexpression of FRS 2 in cells expressing an NGF nonresponsive TrkA receptor mutant reconstitutes the ability of NGF to stop cell cycle progression and to stimulate neuronal differentiation . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The aim of the present study was , using an antibody specific to the high affinity NGF receptor ( trkA ) , to examine immunohistochemically the distribution of the NGF receptor in the mouse olfactory tract , under normal conditions and during regenerative processes . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This suggests the possible involvement of endogenous NGF , acting through its receptor TrkA , in the maintenance of central nervous system cholinergic synapses in the adult rat brain . ^^^ To test this hypothesis , a small peptide , C ( 92 96 ) , that blocks NGF TrkA interactions was delivered stereotactically into the rat cortex over a 2 week period , and its effect and potency were compared with those of an anti NGF monoclonal antibody ( mAb NGF 30 ) . ^^^ However , both mAb NGF 30 and the TrkA antagonist C ( 92 96 ) provoked a significant decrease in the number and size of vesicular acetylcholine transporter IR sites , with the losses being more marked in the C ( 92 96 ) treated rats . ^^^ These observations support the notion that endogenously produced NGF acting through TrkA receptors is involved in the maintenance of the cholinergic phenotype in the normal , adult rat brain and supports the idea that NGF normally plays a role in the continual remodeling of neural circuits during adulthood . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Binding of nerve growth factor ( NGF ) to the trkA tyrosine kinase receptor results in receptor homodimer formation , transphosphorylation , and kinase activation that supports neuronal differentiation and survival . ^^^ We have shown previously that short term exposure of PC 12 cells to brain derived neurotrophic factor or to C 2 ceramide activates a signaling pathway that results in serine phosphorylation of the trkA intracellular domain and reduces the ability of trkA to respond to NGF . ^^^ Here we demonstrate that extended C 2 ceramide exposure dramatically increases NGF induced trkA activation and further show that C 2 ceramide augments trkA tyrosine phosphorylation even in the absence of neurotrophin . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We confirm that NGF restores SNS / PN3 mRNA levels in DRG neurons in vitro and demonstrate that the trk antagonist K252a blocks this rescue . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immunoreactivity for the NGF receptors trkA and p 75 ( NTR ) was decreased and increased , respectively , between days 3 and 28 in right atria from diabetic rats and returned to pretreatment levels at day 49 . ^^^ The ability of NGF to promote regeneration of noradrenergic nerves is lost in diabetes and this may relate to the loss of trkA receptor on prejunctional nerve terminals after denervation . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF also down regulates its own high affinity trkA receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Human TRKA encodes a high affinity tyrosine kinase receptor for nerve growth factor ( NGF ) , a member of the neurotrophin family that induces neurite outgrowth and promotes survival of embryonic sensory and sympathetic neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Therefore , we examined the effect of forced expression of HES 1 and MASH 1 upon nerve growth factor ( NGF ) induced differentiation in TrkA transfected hippocampal neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
SK N BE neuroblastoma cell clones transfected with p 75 ( NTR ) and lacking Trk neurotrophin receptors , previously reported to undergo extensive spontaneous apoptosis and to be protected by nerve growth factor ( NGF ) ( Bunone , G . , Mariotti , A . , Compagni , A . , Morandi , E . , and Della Valle , G . ( 1997 ) Oncogene 14 , 1463 1470 ) , are shown to exhibit ( 1 ) increased levels of the pro apoptotic lipid metabolite ceramide and ( 2 ) high activity of caspases , the proteases of the cell death cascade . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have identified a novel nonpeptidic molecule , ALE 0540 , that inhibits the binding of NGF to tyrosine kinase ( Trk ) A or both p 75 and TrkA ( IC 50 5 . 88 + / 1 . 87 microM , 3 . 72 + / 1 . 3 microM , respectively ) , as well as signal transduction and biological responses mediated by TrkA receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The expression levels of NGF and trkA mRNAs in these cortical areas were too low to determine quantitatively . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These results suggest that trkB agonists BDNF and NT 4 / 5 as well as the trkA agonist NGF can regulate nociceptive responses to noxious heat . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The induction of growth inhibition and differentiation of a glioma cell line by transfection of trk A cDNA was examined , and production of endogenous nerve growth factor ( NGF ) also was studied in these cells . ^^^ When human trk A cDNA was transfected into a human glioma cell line , U 251MG , which lacks expression of both endogenous trk A and low affinity NGF receptor , the transfectant expressed the exogenous trk A mRNA and a functional high affinity NGF receptor . ^^^ In summary , our data suggest that endogenous NGF secreted by glioma cells has an important role in the induction of glioma cell differentiation occuring with transfer of exogenous trk A cDNA . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Demonstration of high levels of the low affinity neurotrophin receptor p 75 but not the high affinity TrkA receptor on the Bcl 2 transfected cell lines suggested that the NGF induced killing was mediated by p 75 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have analyzed the effect of severe traumatic brain injury ( TBI ) on the levels of mRNA expression of neurotrophic factors ( NTFs ) : brain derived neurotrophic factor ( BDNF ) , nerve growth factor ( NGF ) , ciliary neurotrophic factor ( CNTF ) and their respective receptors : trkB , trkA and CNTFRalpha . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In this report , we provide evidence that NGF and BDNF have functionally antagonistic actions on sympathetic neuron growth and target innervation , with NGF acting via TrkA to promote growth and BDNF via p75NTR to inhibit growth . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To investigate a putative role of nerve growth factor ( NGF ) in central plasticity linked to chronic pain , modifications in immunoreactivity ( IR ) for the high affinity NGF receptor , TrkA , were studied at spinal levels in a rat model of inflammatory chronic pain , adjuvant induced arthritis ( AIA ) . ^^^ Enhanced numbers of TrkA IR neurons during AIA strongly support the hypothesis of a participation of NGF in adaptive mechanisms of central nociceptive pathways observed in chronic pain states . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In this review , we will overview the evidence implicating specific signaling cascades in aspects of the cellular response to the neurotrophins , specifically in response to activation of TrkA by NGF . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The neurotrophins NGF , BDNF , NT 3 , and NT 4 each bind to the p 75 receptor and also more selectively to members of the Trk family of receptor tyrosine kinases . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF acts via binding to a specific tyrosine kinase receptor ( TrkA ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Experiments utilizing Trk receptor bodies , K252a , and overexpression of nerve growth factor ( NGF ) demonstrated that these effects were mediated by secreted BDNF interacting with extracellular TrkB receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Expression of rat TrkA in Xenopus spinal neurons confers responsiveness of these neurons to nerve growth factor ( NGF ) in assays of neuronal survival and growth cone chemotropism . ^^^ Mutational analysis indicates that coactivation of phospholipase C gamma ( PLC gamma ) and phosphoinositide 3 kinase ( PI 3 kinase ) by specific cytoplasmic domains of TrkA is essential for triggering chemoattraction of the growth cone in an NGF gradient . ^^^ Uniform exposure of TrkA expressing neurons to NGF resulted in a cross desensitization of turning responses induced by a gradient of netrin 1 , brain derived neurotrophic factor ( BDNF ) , or myelin associated glycoprotein ( MAG ) but not by a gradient of collapsin 1 / semaphorin III / D or neurotrophin 3 ( NT 3 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We also examined these cell lines for presence of TrkA receptor , the high affinity receptor for nerve growth factor ( NGF ) , the prototypic neurotrophin . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Whereas the N 4 , L 38 , and NGFbeta peptide domains present within pro NGF were previously shown to induce phosphorylation of the high affinity NGF receptor , tropomyosin receptor kinase ( Trk ) , only the NGFbeta moiety was able to stimulate anchorage independent growth of prostate tumor cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Most of the biological effects of nerve growth factor ( NGF ) are mediated by TrkA , the high affinity receptor for NGF . ^^^ The early decrease of trkA mRNA is likely due to deprivation of target derived NGF , which is caused by nerve ligation , and the recovery might be because substitute sources of NGF become available . ^^^ Despite the decline in trkA mRNA in the ganglion , 3000 injured DRG neurons sustain TrkA immunoreactivity , suggesting that exogenous NGF can still influence these TrkA expressing neurons , even though they are isolated from the periphery . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To determine whether this action of NGF is mediated by the p140TrkA NGF receptor ( a member of the Trk tyrosine kinase family ) we used a murine basal forebrain cholinergic cell line , SN 56 , stably transfected with rat trkA cDNA . ^^^ Treatment of these transfectants with NGF activated mitogen activated protein kinase and increased cytosolic free calcium concentrations , confirming the reconstitution of TrkA mediated signalling pathways . ^^^ The expression of ChAT and VAChT mRNA , as well as ACh content , were coordinately up regulated by NGF in SN 56 trkA transfectants . ^^^ None of these responses occurred in the parental SN 56 cells , which do not express endogenous TrkA , indicating that these actions of NGF required TrkA . ^^^ The combined treatment of SN 56 trkA cells with CNTF and NGF revealed a complex interaction of these factors in the regulation of cholinergic gene locus expression . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Analyses of the compartmental distributions of the p 75 and trkA NGF receptors themselves do not provide an explanation for the differential cholinergic maturation in the compartments of the control striatum or for the upregulation of CHAT in the striatal matrix after the NGF infusion . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Thus , without p75NTR , NT 3 substitutes for NGF , suggesting that p 75 alters the neurotrophin specificity of TrkA in vivo . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Three trk receptor subtypes are known at present , trk A , trk B and trk C , which preferentially bind NGF , BDNF and NT 3 respectively . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Many nociceptive dorsal root ganglion ( DRG ) sensory neurons express the high affinity nerve growth factor ( NGF ) receptor TRKA , and respond to NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These results reveal a role for NF kappaB in regulating neuronal survival during embryonic development and suggest that in addition to the well established Trk receptor tyrosine kinase signaling cascade , NGF enhances neuronal survival by signaling via a p 75 mediated pathway . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Identical results were obtained when a specific agonist of the NGF receptor TrkA , the bivalent anti rat TrkA IgG ( RTA ) , was infused into the cortex in place of NGF . ^^^ We conclude that NGF signalling via the TrkA receptor must be coupled to afferent electrical activity to produce its effects on the eye preference of cortical neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Trk ( def ) was kinase active but defective for NGF induced responses when stably expressed in PC12nnr5 cells ( which lack detectable levels of TrkA and are non responsive to NGF ) . ^^^ NGF stimulated tyrosine phosphorylation of the Trk ( def ) +PI 3 kinase addback receptor , resulted in the direct association and selective activation of PI 3 kinase in vitro and the production of PI ( 3 , 4 ) P 2 and PI ( 3 , 4 , 5 ) P 3 in vivo ( comparable to wild type ) . ^^^ PC12nnr5 cells stably expressing Trk ( def ) + PI 3 kinase , initiated neurite outgrowth but failed to stably extend and maintain these neurites in response to NGF as compared to PC 12 parental cells , or PC12nnr5 cells overexpressing wild type Trk . ^^^ However , Trk ( def ) + PI 3 kinase was fully competent in mediating NGF induced survival processes . ^^^ Trk ( def ) was kinase active but defective for NGF induced responses when stably expressed in PC12nnr5 cells ( which lack detectable levels of TrkA and are non responsive to NGF ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To understand the mechanism of neurotrophin stimulated calcium uptake , the regulation of calcium uptake and intracellular mobilization by nerve growth factor ( NGF ) was investigated using NIH 3T3 cells stably transfected with either the high affinity NGF receptor p 140 ( trk ) ( 3T3 Trk ) or the low affinity NGF receptor p 75 ( NGFR ) ( 3T3 p 75 ) . ^^^ In 3T3 Trk cells , NGF increased both calcium uptake and intracellular calcium mobilization . ^^^ Nifedipine , an inhibitor of calcium uptake through L type calcium channels , inhibited the action of NGF on both 3T3 Trk cells and 3T3 p 75 cells , indicating that both p 140 ( trk ) and p 75 ( NGFR ) receptors are linked to nifedipine sensitive L type calcium channels . ^^^ These studies show that either NGF receptor will support increases in intracellular calcium but that p 140 ( trk ) does so by increasing both uptake and mobilization , whereas p 75 ( NGFR ) does so by increasing uptake only . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
SH 2 B has been shown to be required for nerve growth factor ( NGF ) mediated neuronal differentiation and survival , associate with NGF receptor TrkA , and be tyrosyl phosphorylated in response to NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The translocation of SC 1 to the nucleus was specific for p 75 , as NGF binding to the TrkA receptor did not lead to nuclear localization of SC 1 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) , the prototypic member of the neurotrophin family of growth factors , exerts its action via two receptors , P75NTR and TrkA , the expression of which varies at the cell surface of neuroblastoma cells ( SH SY5Y cells ) in a cycle phase specific manner . ^^^ NGF was pro apoptotic on growing cells expressing preferentially P75NTR and exhibited a potent anti apoptotic effect on quiescent cells , when TrkA was prevalent at the cell surface , showing that NGF can have a dual action on SH SY5Y cells depending on the relative cell surface expression of TrkA and P75NTR . ^^^ On the other hand , we showed that the anti apoptotic activity of NGF was specifically mediated by an interaction with TrkA with no contribution of P75NTR , as demonstrated on SK N BE cells transfected with TrkA in which NGF was a potent anti apoptotic compound but did not exhibit any pro apoptotic activity . ^^^ These results support the hypothesis that the survival response to NGF depends on its binding to TrkA without any involvement of P75NTR which in turn selectively mediates the pro apoptotic activity of NGF with no contribution of TrkA and show that , depending on the growth state of the cells , NGF exhibits dual pro or anti apoptotic properties via P75NTR and TrkA , respectively . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have shown recently in the pheochromocytoma PC 12 cell line , that the activation of the high affinity receptor for nerve growth factor ( NGF ) , tyrosine kinase receptor ( TrkA ) , results in increased secretion of the amyloid precursor protein ( APP ) into the culture medium . ^^^ In order to reveal through which TrkA associated signaling pathway the secretory APP processing is mediated , signaling cascades activated by TrkA stimulation were selectively inhibited under conditions of selective TrkA stimulation via non NGF mechanisms and APP secretion into the culture medium was followed by Western analysis . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Signal transduction of nerve growth factor ( NGF ) and its TrkA and p75NTR receptors ] . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF receptor ( TrkA and p75NGFR ) expression was investigated in human thymuses , including normal thymuses , thymic hyperplasias , thymomas and thymic carcinomas . ^^^ A switch from the normal TrkA positive p75NGFR negative phenotype to a TrkA negative p75NGFR positive phenotype was found in histologically aggressive epithelial cell tumors , suggesting that NGF and its receptors are potentially involved in thymus stroma organogenesis and proliferation . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These events are mediated by NGF as a result of binding to its two cell surface receptors , TrkA and p 75 . ^^^ TrkA is a receptor with tyrosine kinase activity that forms a high affinity binding site for NGF . ^^^ Of the five domains comprising its extracellular portion , the immunoglobulin like domain proximal to the membrane ( TrkA d 5 domain ) is necessary and sufficient for NGF binding . ^^^ Here we present the crystal structure of human NGF in complex with human TrkA d 5 at 2 . 2 A resolution . ^^^ One patch involves the central beta sheet that forms the core of the homodimeric NGF molecule and the loops at the carboxy terminal pole of TrkA d 5 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) treatment of Chinese hamster ovary fibroblast ( CHO ) cells exogenously expressing 2 . 5x105 TrkA receptors ( CHO / TrkA ) results in inhibition of serum and insulin like growth factor 1 ( IGF 1 ) stimulated cell proliferation in a dose dependent manner . ^^^ Furthermore , NGF does not stimulate [ 3H ] thymidine incorporation and inhibits IGF 1 mediated DNA synthesis in CHO / TrkA cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the testis of an 18 wk gestational age human fetus , immunohistochemical analysis has shown intense immunoreactivity of mesenchymal cells to antibodies for neurotrophin receptors p 75 , trk A , and trk C , and their ligands NGF and NT 3 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
During a critical period of late prenatal development nerve growth factor ( NGF ) signalling through its cognate high affinity receptor trkA has been shown to be the main survival factor during a critical period of prenatal development . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Characterization of an NGF P TrkA retrograde signaling complex and age dependent regulation of TrkA phosphorylation in sympathetic neurons . ^^^ NGF promotes growth and survival of neurons via activation of the receptor tyrosine kinase TrkA . ^^^ Our results demonstrate that an NGF phospho TrkA ( NGF P TrkA ) signaling complex forms in distal axons and is retrogradely transported as a complex to cell bodies of sympathetic neurons . ^^^ Although a minor fraction of both NGF and TrkA is retrogradely transported , a large fraction of the NGF that is retrogradely transported is found complexed with retrogradely transported TrkA . ^^^ Interestingly , the metabolism of the P TrkA complex is dramatically different in young , NGF dependent sympathetic neurons as compared to older , NGF independent sympathetic neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Acute stimulation of RA predifferentiated SH SY5Y cells with brain derived neurotrophic factor ( BDNF ) , neurotrophin 3 ( NT 3 ) , or neurotrophin 4 / 5 ( NT 4 / 5 ) , but not nerve growth factor ( NGF ) , induces Trk autophosphorylation , followed by phosphorylation of Akt and the extracellular signal regulated kinases ( ERKs ) 1 and 2 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Tyrosine kinase A ( TrkA ) , a high affinity receptor for nerve growth factor ( NGF ) , is activated during differentiation and regeneration of selective neuronal population . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) induces differentiation of the rat pheochromocytoma clone ( PC 12 ) by activating the high affinity receptor , p 140 ( trkA ) , linked to mitogen activated protein kinase . ^^^ In this study , we determined whether TrkA or p 75 is involved in NGF mediated regulation of A ( 2A ) AR expression . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The capacity for the neurotrophic factor PACAP 38 to regulate expression of nerve growth factor ( NGF ) trkA receptors in PC 12 cells has been examined . ^^^ PACAP 38 provoked an increase in basal and NGF stimulated phosphorylation of trkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
However , the up regulation of insulin like growth factor 2 ( IGF 2 ) expression is a predominant feature of trkA activation by nerve growth factor ( NGF ) . ^^^ The growth inhibition induced by blocking the insulin like growth factor 1 receptor suggests that IGF 2 is a component of the effector mechanism of trkA activation by NGF in trkA transfected cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Treatment of serum deprived PC 12 with NGF induced persistent AP 1 binding activity that was blocked by the Trk receptor inhibitor K252a . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These data show distinct colocalizations of TrkA with specific neurochemicals in vagal and glossopharyngeal sensory neurons , and suggest that nerve growth factor ( NGF ) , the neurotrophin ligand for TrkA , plays a role in functions of specific neurochemically defined subpopulations of mature vagal and glossopharyngeal sensory neurons . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
A population of adult dorsal root ganglion ( DRG ) neurons bind NGF with high affinity and express the trkA gene . ^^^ The current study examined further this potential collaboration in the DRG by determining the effect of short term estrogen replacement in OVX rats on DRG trkA mRNA levels following sciatic nerve transection and the resulting removal of a vital source of NGF for those cells . ^^^ Moreover , the current data show that estrogen regulates trkA mRNA levels in the absence of target derived NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Trk A IR was detected at just moderate levels during 5 and 7 weeks reflecting the presence of NGF high affinity receptors only at these earlier developmental ages . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The ganglioside GM 1 is known to protect neuronal cell lines from apoptosis induced by serum / growth factor withdrawal and its effect is mediated in part by the direct activation of the trkA NGF receptor [ G . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The trkA proto oncogene encodes a high affinity NGF receptor that is essential for the survival , differentiation and maintenance of many neural and non neural cell types . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have exploited a new monoclonal antibody against the tyrosine kinase A ( TrkA ) nerve growth factor ( NGF ) receptor to block the NGF TrkA interaction in the rat basal forebrain . ^^^ The monoclonal antibody MNAC 13 is a potent antagonist that prevents the binding of NGF to TrkA in a variety of systems . ^^^ When antibody secreting cells are implanted at postnatal day 2 ( P 2 ) , the effects observed at P 8 are as severe as those obtained with anti NGF antibodies and , interestingly , are observed also if anti TrkA cells are implanted at P 8 , when anti NGF antibodies , delivered by the same route , are no longer effective ( ) . ^^^ The effects induced by anti TrkA , as those induced by anti NGF , are reversible , but the time required for recovery and the critical period in the sensitivity of BFCNs to the functional inactivation of TrkA is twice as long than that observed when NGF is intercepted . ^^^ These results demonstrate that BFCNs are more sensitive to the block of TrkA activation than they are to the block of NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The data indicate that NGF , in the presence of trans 1 aminocyclopentyl 1 , 3 dicarboxylate ( ACPD ) , enhanced KCI stimulated release and KCI stimulated calcium influx in vitro and that these effects were blocked by the tyrosine receptor kinase ( trk ) inhibitor tyrphostin AG 879 . ^^^ The data also indicate that NGF increased phosphorylation of trkA and the mitogen activated protein kinase extracellular signal regulated kinase ( ERK ) in dentate gyrus in vitro . ^^^ These findings are consistent with the hypothesis that NGF , by interacting with trkA , triggers a sequence of tyrosine kinase dependent phosphorylation steps that modulate glutamate release and calcium influx and impact on expression of LTP in dentate gyrus . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) and its high affinity tyrosine kinase receptor A ( TrkA ) are involved in neural development and survival and growth of central and peripheral nerves . ^^^ RESULTS : By Northern blot analysis , NGF and TrkA mRNA expression were increased in 42 % ( 13 . 1 fold ) and 54 % ( 5 . 5 fold ) of the CP samples ( p < 0 . 01 ) , respectively . ^^^ Further , enhanced NGF and TrkA mRNA signals were also present in intrapancreatic ganglia cells in CP samples . ^^^ Analysis of the molecular findings with clinical parameters revealed a significant relation ( p < 0 . 05 ) between NGF mRNA levels and pancreatic fibrosis ( r = 0 . 64 ) and acinar cell damage ( r = 0 . 74 ) and between TrkA mRNA and pain intensity ( r = 0 . 84 ) . ^^^ CONCLUSION : Activation of the NGF / TrkA pathway occurs in CP . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Overexpression of MIR cDNA in PC 12 cells abrogated neurite outgrowth induced by nerve growth factor ( NGF ) without affecting TrkA signaling . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) binding to its receptors TrkA and p 75 ( NTR ) enhances the survival , differentiation , and maintenance of neurons . ^^^ Binding and cross linking studies demonstrated that the NGF binding to both TrkA and p 75 ( NTR ) was considerably enriched in CLM and that about 90 % of high affinity binding to TrkA was present in CLM . ^^^ When PC 12 cells were treated with NGF , virtually all activated ( i . e . tyrosine phosphorylated ) TrkA was found in the CLM . ^^^ Remarkably , in NGF treated cells , it was only in CLM that activated TrkA was coimmunoprecipitated with phosphorylated Shc and PLCgamma . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) and its high affinity receptor TrkA are involved in stimulating epithelial cancer cell growth and perineural invasion , as well as in pain generation in chronic benign disorders . ^^^ PATIENTS AND METHODS : NGF and TrkA were examined by Northern blot analysis , in situ hybridization , and immunohistochemistry in 27 normal and 37 pancreatic cancer tissue samples . ^^^ RESULTS : Northern blot analysis indicated that NGF and TrkA mRNA levels were increased 2 . 7 fold and 5 . 6 fold , respectively ( P < . 05 and P < . 05 ) , in pancreatic cancer tissues compared with the normal pancreas tissue . ^^^ There was no difference in NGF and TrkA expression between early ( stages 1 and 2 ) and advanced ( stage 3 ) tumor stages and between well / moderately differentiated ( grades 1 and 2 ) and poorly differentiated ( grade 3 ) tumors . ^^^ However , tumors with high NGF / TrkA expression levels exhibited more frequent perineural invasion ( P < . 01 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The expression of the mutated constructs into COS 1 cells revealed that the introduced mutation , while not affecting its correct membrane localization , rendered the NTRK 1 protein unable to undergo activation upon stimulation with NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Human monocytes / macrophages ( M / M ) infected in vitro with HIV type 1 ( HIV 1 ) are able to produce substantial levels of NGF that are associated with enhanced expression of the high affinity NGF receptor ( p 140 trkA ) on the M / M surface . ^^^ Treatment of HIV infected human M / M with anti NGF Ab blocking the biological activity of NGF leads to a marked decrease of the expression of p 140 trkA high affinity receptor , a concomitant increased expression of p 75 ( NTR ) low affinity receptor for NGF , and the occurrence of apoptotic death of M / M . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To define cellular mechanisms that modulate A ( 2A ) AR expression , A ( 2A ) AR mRNA and protein levels were examined in three PC 12 sublines : 1 ) PC12nnr5 cells , which lack the high affinity NGF receptor TrkA , 2 ) srcDN 2 cells , which overexpress kinase defective Src , and 3 ) 17 . 26 cells , which overexpress a dominant inhibitory Ras . ^^^ In the absence of functional TrkA , Src , or Ras , NGF induced down regulation of A ( 2A ) AR mRNA and protein was significantly impaired . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The neurotrophin receptor ( p75NTR ) is best known for mediating tropic support by participating in the formation of high affinity nerve growth factor ( NGF ) receptor complexes with trkA , however , p75NTR more recently has been shown to act as a bona fide death signaling receptor , which can signal independently of trkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Apart from its high affinity receptor TrkA , nerve growth factor ( NGF ) can also stimulate the low affinity receptor p 75 ( LNTR ) and induce a Trk independent signaling cascade . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Anandamide ( ANA ) inhibits prolactin and nerve growth factor ( NGF ) induced proliferation of human breast cancer cells by decreasing the levels of the 100 kDa prolactin receptor ( PRLr ) and the high affinity trk NGF receptor , respectively , and by acting via CB ( 1 ) like cannabinoid receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Here we report that 1 ) anandamide and 2 AG inhibit the nerve growth factor ( NGF ) induced proliferation of HBCCs through suppression of the levels of NGF Trk receptors ; 2 ) inhibition of PRLr levels results in inhibition of the proliferation of other PRL responsive cells , the prostate cancer DU 145 cell line ; and 3 ) CB 1 like cannabinoid receptors are expressed in HBCCs and DU 145 cells and mediate the inhibition of cell proliferation and Trk / PRLr expression . ^^^ Anandamide and HU 210 exerted a strong inhibition of the levels of NGF Trk receptors as detected by Western immunoblotting ; this effect was reversed by SR141716A . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To investigate further its possible mode of action , the ability of monoamine activated alpha1M and normal alpha1M to bind and to activate the NGF receptor ( TrkA ) was investigated . ^^^ Monoamine activated alpha1M formed a more stable complex with TrkA than normal alpha 1 M , but the binding of monoamine activated alpha1M to TrkA was adversely affected by prior stimulation of TrkA with NGF . ^^^ In addition , monoamine activated alpha1M enhanced the NGF promoted TrkA phosphorylation and up regulated the expression of NGF inducible immediate early genes ( c jun and NGFI A ) and delayed response genes ( SCG 10 and transin ) in PC 12 cells ; normal alpha1M , in contrast , produced little or no effect . ^^^ This study demonstrates that alpha1M , the constitutive form of alpha macroglobulin in the rat , possesses the ability to promote NGF mediated differentiation in PC 12 cells , possibly via its direct action on TrkA receptors and TrkA mediated signal transduction and gene expression . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) induces apoptosis in a human medulloblastoma cell line ( MED 283 ) engineered to express TrkA ( MED 283 TrkA ) ( Muragaki , Y . , Chou , T . ^^^ We found that MED 283 TrkA cells expressing a dominant negative Ras inhibitor ( N17Ras ) failed to undergo ERK activation and apoptosis following NGF treatment , whereas the ERK kinase ( mitogen activated protein kinase kinase ) inhibitors PD 98059 and U 0126 eliminated ERK activation but had no effect on apoptosis . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA is the receptor tyrosine kinase ( RTK ) for nerve growth factor ( NGF ) and stimulates NGF dependent cell survival and differentiation in primary neurons . ^^^ TrkA expression in neuronal tumors also supports NGF dependent differentiation of neuroblastomas and apoptosis of medulloblastomas . ^^^ The strongest constitutively active TrkA mutants , GluAsp and AspGlu , support NGF independent neuritogenesis and cell survival to levels approximately 65 and 80 100 % , respectively , of NGF activated wild type TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
However , during development precursors to rat sympathetic neurons in the thoracolumbar region are not responsive to NGF because they lack the signal transducing NGF receptor , trkA . ^^^ We have previously shown that acquisition of trkA expression is sufficient to confer a functional response to NGF . ^^^ Finally , we identify a subpopulation of sympathetic neuroblasts in the thoracolumbar region whose survival , exit from the cell cycle , induction of trkA expression , and consequent acquisition of NGF responsiveness in culture appear to be neurotrophin independent and cell autonomous . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
K 252 , a specific inhibitor of trk phosphorylation , blocks NGF induced keratinocyte proliferation , in absence of exogenous NGF . ^^^ Normal keratinocytes over expressing TrkA proliferate better than control transfectants , while the NGF mimicking anti Trk antibody induces an increased keratinocyte proliferation in Trk over expressing cells as compared to mock transfected keratinocytes . ^^^ Because NGF and Trk levels are highly expressed in psoriasis . one could speculate that NGF autocrine system plays a role in the mechanisms associated with this and other hyperproliferative skin conditions , including cancer . . ^^^ Keratinocytes express both the low ( p 75 ) and the high affinity ( TrkA ) NGF receptors , which are located in the basal layer of the epidermis . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Moreover , the results showed that the optic nerves also expressed trkA NGF receptor and NGFmRNA , most likely by oligodendrocytes , implying that NGF is locally produced and suggesting that the presence of NGF might be regulated by an autocrine mechanism . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
While FGFR 1 interacts with FRS 2 constitutively , independent of ligand stimulation and tyrosine phosphorylation , NGF receptor ( TrkA ) binding to FRS 2 is strongly dependent on receptor activation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) the founding member of the neurotrophin family , binds to two types of receptors : Trk tyrosine kinase and the p 75 neurotrophin receptor , which belongs to the Fas tumor necrosis factor ( TNF ) receptor superfamily . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Expression of wild type p75NTR created a state of neurotrophin dependence : cells could be rescued by nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , or neurotrophin 3 ( NT 3 ) , but not by a mutant NGF that binds well to Trk A but poorly to p75NTR . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) , another neurotrophin which acts via the trkA receptor , was also studied . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
RT PCR analysis revealed the presence of p 75 and trkB transcripts in cortical cultures , but did not detect transcripts of trkA , a high affinity receptor for NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) initiates the majority of its biological effects by promoting the dimerization and activation of the tyrosine kinase receptor TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) is known to exert a mitogenic effect on human breast cancer cells through proto TrkA activation . ^^^ While cytofluorimetric and Western blot analysis indicated proto TrkA expression in three of the four cell lines , NGF stimulated growth in only two of the three positive cell lines . ^^^ Inhibition of NGF induced MAPK activation by an antibody directed against the extracellular domain of TrkA but not by an inhibitor of TrkA phosphorylation demonstrated the requirement of NGF binding but not of proto TrkA kinase activity for MAPK activation , suggesting the recruitment of another kinase for transmission of the mitogenic signaling . ^^^ Down modulation of p 185 ( HER 2 ) expression in a breast carcinoma line transfected with a construct containing an anti p 185 ( HER 2 ) antibody sequence and expressing proto TrkA impaired NGF induced MAPK activation and proliferation . ^^^ Together these data show that in cells expressing low levels of TrkA such as breast carcinoma cells , NGF must recruit other overexpressed receptors such as p 185 ( HER 2 ) in order to generate a biological signal that can induce breast cancer cell growth . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In these transfectant cells , a continuous phosphorylation of TrkA and the activation of ERK1 / 2 without NGF treatment were observed . ^^^ A TrkA dimer was detected in the GD 3 synthase transfectant cells regardless of NGF treatment by cross linking and immunoblotting . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
While MC CM raised mRNA for trkA , the effect was not synergistic with NGF . mRNA for the common neurotrophin receptor ( p75NTR ) showed a modest synergistic increase . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This effect of BDNF is mimicked by NT 4 , but not NGF , and blocked by the Trk tyrosine kinase inhibitor K252a , consistent with a requirement for TrkB receptor activation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Using univariant statistics we demonstrated that in LM / Bc embryos with NTDs , the expression of bdnf , ngf , and trk , ngf R were significantly elevated at all three time points , and the cytokine , cntf was significantly decreased at GD 9 : 00 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Many responses to nerve growth factor ( NGF ) are regulated through the receptor tyrosine kinase trkA . ^^^ To understand more fully the functions of trkA in NGF responsive cells , we have expressed the intracellular domain of rat trkA as a fusion protein with the yeast gal 4 transcription factor , and used the fusion protein to probe rat and mouse cDNA libraries by the yeast two hybrid system . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Human keratinocytes also synthesize and express the low ( p 75 ) and the high affinity ( trk ) NGF receptor ( NGF R ) . ^^^ NGF stimulates keratinocyte proliferation which is blocked by the natural alcaloid K 252 , a specific inhibitor of trk phosphorylation . ^^^ K 252 inhibits keratinocyte proliferation and induces keratinocyte apoptosis , in the absence of exogenous NGF , indicating the existence of an autocrine loop where NGF and trk act as key players . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
For example , nearly 70 % of the NGF , BDNF , and NT 3 positive neurons in layer 5 colabeled with their respective high affinity receptors , i . e . , trkA , trkB , and trkC , respectively . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In glial cells and some neurons that express p 75 but not TrkA , p 75 causes cell death in response to nerve growth factor ( NGF ) binding . ^^^ Another major challenge is to develop a model that reconciles the different facets of p 75 , such as its ability in some situations to assist TrkA to rescue NGF dependent neurons , but to stimulate apoptosis in others . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Because PMCs constitutively express the NGF high affinity receptor ( TrkA ) with a tyrosine kinase domain , we focused on downstream effectors in signaling cascades following the TrkA . ^^^ These findings suggested that NGF initiated chemotactic movement of PMCs through both MAPK and PI3K signaling pathways following TrkA activation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Blocking the NGF TrkA interaction rescues the developmental loss of LTP in the rat visual cortex : role of the cholinergic system . ^^^ At later postnatal ages , blockade of either endogenous NGF by immunoadhesin ( TrkA IgG ) or TrkA receptors by monoclonal antibody rescues LTP . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In normal skin , nerve growth factor ( NGF ) is produced by basal keratinocytes , and acts via its high affinity receptor ( trk A ) on nociceptor nerve fibres to increase their sensitivity , particularly in inflammation . ^^^ We have therefore studied NGF and trk A like immunoreactivity in affected skin and mirror site clinically unaffected skin from patients with leprosy , and compared these with non leprosy , control skin , following quantitative sensory testing at each site . ^^^ Keratinocyte trk A expression ( which mediates an autocrine role for NGF ) was increased in clinically affected and unaffected skin , suggesting a compensatory mechanism secondary to reduced NGF secretion at both sites . ^^^ Sensory loss occurred with reduced sub epidermal nerve fibres in affected skin , but these still showed trk A staining , suggesting NGF treatment may restore pain sensation . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Development of sensory neurons in the absence of NGF / TrkA signaling in vivo . ^^^ To study peripheral neuron development in the absence of neurotrophin signaling , we have generated mice that are double null for BAX and nerve growth factor ( NGF ) , and BAX and the NGF receptor TrkA . ^^^ All dorsal root ganglion ( DRG ) neurons that normally die in the absence of NGF / TrkA signaling survive if BAX is also eliminated . ^^^ These findings establish that NGF / TrkA signaling regulates peripheral target field innervation and is required for the full phenotypic differentiation of sensory neurons . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These results suggest that simvastatin is neurotoxic and PC 12 cells elicited a protective response , involving a transient activation of a Trk mediated intracellular signal transduction pathway by an autocrine secretion of NGF , although these responses did not persist against pro apoptotic signals and resulted in an apoptosis of the PC 12 cells . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
METHODS : Transcription of nerve growth factor ( NGF ) , neurotrophin 3 ( NT 3 ) , NT 4 , brain derived neurotrophic factor ( BDNF ) , glial cell line derived neurotrophic factor ( GDNF ) , and receptors Trk A E , was investigated by reverse transcription polymerase chain reaction . ^^^ RESULTS : Transcription of NGF , NT 3 , BDNF , and Trk A , Trk B , Trk C , and Trk E receptors was detected in both ex vivo and cultured epithelium and stroma . ^^^ Levels of transcription were higher for NT 3 , NT 4 , and the Trk receptors and lower for NGF , BDNF , and GDNF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA , the NGF receptor tyrosine kinase , was expressed in the nodose ganglion throughout development and there was a marked decrease in TrkA mRNA expression in the nodose ganglion of NGF / embryos . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Only the TrkA and not the p 75 NGF receptor was detected at m RNA and protein level , and only the TrkA NGF receptor was up regulated during NGF driven culture . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Recent evidence indicates that nerve growth factor ( NGF ) produces its effects through signaling contributions from both TrkA and the p 75 receptor . ^^^ In contrast to its trophic actions through TrkA , NGF binding to p 75 has been shown to activate programmed cell death through a mechanism involving the stress kinase JNK . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Although the individual amino acids in TrkA involved in binding to nerve growth factor ( NGF ) and those in TrkC involved in binding to neurotrophin 3 have been mapped in this domain , the Trk amino acids that provide specificity remained unclear . ^^^ The resulting Trk variant recruited binding of NGF equivalent to TrkA , maintained neurotrophin 3 binding equivalent to TrkC , and also bound brain derived neurotrophin , although with lower affinity compared with TrkB . ^^^ In this study , a minimum set of residues in the human TrkC second immunoglobulin like domain , which does not bind nerve growth factor ( NGF ) , were substituted with those from human TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
On the contrary , cell adhesion , cellular duplication , 5 ' nucleotidase activity , NGF induced tyrosine autophosphorylation of TrkA receptors are not affected . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF stimulated proliferation was inhibited in a dose dependent fashion by K252a , a blocker of Trk induced receptor kinases . ^^^ These data suggest that GBM cell growth can be enhanced by NGF acting via Trk receptor phosphorylation . ^^^ Mitogenesis in glioblastoma multiforme cell lines : a role for NGF and its TrkA receptors . ^^^ Proteins for both the high affinity NGF specific tyrosine kinase binding site ( p140TrkA ; TrkA ) and the low affinity neurotrophin ( p75NTR ) receptor were present in all three GBM cell lines . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) plays a crucial role in synaptic plasticity during brain development and adulthood by activating a dual receptor system composed of TrkA and p 75 ( p75NTR ) receptors . ^^^ The ability of glucocorticoids to increase NGF expression in the hippocampus prompted us to investigate whether the synthetic glucocorticoid dexamethasone ( DEX ) increases TrkA and p75NTR expression in NGF target cholinergic neurons in developing rats . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Here , ( 35 ) S riboprobes were used to determine whether pulpal afferents of adult ( 2 month old ) rats express the nerve growth factor ( NGF ) receptors , p 75 ( NTR ) and trkA , which are characteristic of peptidergic nociceptors , and additionally , whether these cells express receptors ( trkB and trkC ) for other members of the neurotrophin family . ^^^ Consistent with reports that NGF responsive neurones also express BDNF , NGF deprivation resulted in a reduction in the number of pulpal afferents that expressed BDNF to an extent similar to that seen for trkA . ^^^ These findings indicate that most pulpal afferents in the adult express the NGF receptors p 75 ( NTR ) and trkA , and thus have a continuing potential susceptibility to NGF mediated regulation of functions such as neuropeptide and BDNF synthesis . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
High affinity tyrosine kinase A ( trkA ) neurotrophin receptors on neurons and nonneuronal cells elicit differentiation or survival functions in response to nerve growth factor ( NGF ) , whereas the low affinity neurotrophin ( p 75 ) receptor modulates trkA activity or can independently cause apoptosis or NFkappaB mediated survival functions . ^^^ We examined dental tissues for the presence of trkA like immunoreactivity ( trkA IR ) , to determine which nonneuronal cell types express it in normal compared with inflamed teeth and how the trkA positive cells relate to those expressing the p 75 receptor and / or NGF . ^^^ Tooth injury disrupts this system such that trkA IR decreases in injured odontoblasts , p 75 decreases in fibroblasts , and NGF is upregulated by fibroblasts and accumulates in the injured pulp and surviving odontoblasts . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Here , we show that activation of ectopically expressed TrkA , the tyrosine kinase receptor for nerve growth factor ( NGF ) , stimulates embryonal carcinoma P 19 cells to develop extensive intercellular contacts and to assemble into closely packed clusters . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In conjunction , evidence of reduced sympathetic innervation in the failing heart was apparent , as measured histologically by catecholamine fluorescence and by expression of the neuronal NGF receptor trkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
AIMS : To analyse the concomitant presence of NGF and its high affinity receptor TrkA in patients undergoing surgery for Crohn ' s disease ( CD ) and ulcerative colitis ( UC ) . ^^^ METHODS : Expression of NGF and TrkA was studied by northern blot analysis . ^^^ Western blot analysis was used to confirm the specificity of NGF and TrkA antibodies . ^^^ RESULTS : In CD , NGF mRNA was increased in 60 % ( 2 . 4 fold ; p < 0 . 01 ) and TrkA mRNA in 54 % ( 1 . 3 fold ; p < 0 . 05 ) of samples . ^^^ In UC , NGF mRNA expression was enhanced in 58 % ( 2 . 4 fold ; p < 0 . 01 ) and TrkA mRNA expression in 50 % ( 1 . 5 fold ; p < 0 . 05 ) of samples . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
BACKGROUND : Binding of nerve growth factor ( NGF ) to its receptor TrkA leads to intracellular tyrosine kinase activation and regulates the growth and differentiation of various non neuronal tumours . ^^^ PATIENTS AND METHODS : In the present study NGF and TrkA were analysed by Northern blot analysis , in situ hybridisation and immunohistochemistry in 41 esophageal cancer samples in comparison to normal controls . ^^^ RESULTS : NGF mRNA ( P < 0 . 01 ) , but not TrkA mRNA was down regulated in esophageal cancer samples compared with normal tissues . ^^^ In the normal esophagus , NGF mRNA and protein was present in epithelial cells of the entire epithelial layer and TrkA mRNA and protein was present in epithelial cells of the basal layer . ^^^ In esophageal cancer NGF and TrkA mRNA and protein were present in the cancer cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Wild type SH SY5Y cells are unresponsive to nerve growth factor ( NGF ) , but cells transfected with the high affinity NGF receptor TrkA ( SH SY5Y / TrkA ) differentiate in response to NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The discoidin domain receptor ( DDR 1 ) is characterized by a discoidin 1 motif in the extracellular domain , an unusually long cytoplasmic juxtamembrane ( JM ) region , and a kinase domain that is 45 % identical to that of the NGF receptor , TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have recently reported that retinoic acid ( RA ) induced the expression of trkA , the high affinity receptor for nerve growth factor ( NGF ) , in human myeloid leukemia KG 1 cells . ^^^ Furthermore , activation of the induced trkA receptor by exogenous NGF potentiated the differentiating effects of RA and NaBut . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In vitro human and rat corneal epithelial cells produce , store , and release NGF and also express high affinity NGF receptors ( TrkA ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the subacute phase , expression of NGF , BDNF , NT 3 , p75LNGFR and Trk B mRNAs began to increase in the nonneuronal cells and neuronal cells from 6 h , and peaked at 24 72 h in the area where expression of mRNAs for IEGs and cytokines overlapped . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These effects are due to suppression of the levels of the 100 kDa prolactin receptor or of the high affinity NGF receptors ( trk ) , are mediated by CB ( 1 ) like cannabinoid receptors , and are enhanced by other CFADs . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The authors demonstrate for the first time the immunocytochemical expression of the low affinity neurotrophic growth factor ( NGF ) receptor p75LNGFR and the high affinity NGF receptor trkA in the human testis . ^^^ These findings implicate the neurotrophic factor NGF and its receptors p75LNGFR and trkA in the autocrine and paracrine regulation of the steroidogenic activity of Leydig cells of the human testis . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Cholinergic medial septum neurons express TrkA and p 75 nerve growth factor receptor ( p 75 ( NGFR ) ) and interactions between TrkA and p 75 ( NGFR ) are necessary for high affinity binding and signaling of nerve growth factor ( NGF ) through TrkA . ^^^ Here , we investigated whether chronic and long term absence of p 75 ( NGFR ) ( and possibly reduced NGF transport and TrkA binding ) would affect the cholinergic septohippocampal system during aging in mice . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We examined the expression of nerve growth factor ( NGF ) and the low affinity ( p 75 ) and high affinity ( trkA , trkB , and trkC ) neurotrophin receptors in the trigeminal system of adult rats . ^^^ Taken together , these data imply that NGF must be elaborated by neurons that co express both p 75 and trkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Our results also show that the signaling effector SH 2 B is a substrate of NGF mediated Trk signaling in NB , whereas it is not activated by NGF in rat pheochromocytoma PC 12 cells . ^^^ Activation of the neurotrophin receptor TrkA by its ligand nerve growth factor ( NGF ) initiates a cascade of signaling events leading to neuronal differentiation in vitro and might play an important role in the differentiation of favorable neuroblastomas ( NB ) in vivo . ^^^ To study TrkA signal transduction pathways and their effects on differentiation in NB , we stably expressed wild type TrkA and five different TrkA mutants in the NGF unresponsive human NB cell line SH SY5Y . ^^^ Introduction of wild type TrkA restored NGF responsiveness of SH SY5Y cells , as demonstrated by morphological differentiation , activation of mitogen activated protein kinases ( MAPK ) and induction of immediate early genes . ^^^ Expression of TrkA in the absence of NGF resulted in growth inhibition of transfectants compared to parental cells , whereas NGF treatment increased their proliferation rate . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The peripheral expression of trkA encoding for NGF receptor was investigated by RNase protection assay . ^^^ Their combined expression with trkA L 3 transcripts suggests that specific peripheral TrkA oligomers may modulate NGF binding and function in non neuronal cells . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
METHODS : Synovium of 15 patients with RA in active phase and synovium of 14 patients without synovial inflammation were processed for histochemical ( NADPH diaphorase ) and immunohistochemical visualization of different isoforms for the NO synthesis enzyme NO synthase ( NOS ) and for NGF high affinity receptor trkA . ^^^ In the same areas and in the same cell types , although not in the same cells , we also found positivity for the NGF high affinity receptor trkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The receptor tyrosine kinase Kit thus contrasts with the receptor tyrosine kinase trkA , which is activated by the sprouting stimulus ( NGF ) but not by the axonal regeneration signal . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
However , pretreatment with anti NGF antibody or TrkA inhibitor AG 879 profoundly raised KA toxicity . ^^^ These results indicate that in developing cortical neurons , activation of AMPA / KA receptors by KA may induce expression , followed by activation of TrkA via PLC signaling and intracellular calcium elevation and hence increase reception of NGF on KA challenged neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Effect of streptozotocin induced diabetes on NGF , P 75 ( NTR ) and TrkA content of prevertebral and paravertebral rat sympathetic ganglia . ^^^ To test this hypothesis , we measured NGF content and NGF receptor expression , p 75 ( NTR ) ( low affinity neurotrophin receptor ) and trkA ( high affinity NGF receptor ) , in control and diabetic rat SMG , CG and superior cervical ganglia ( SCG ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Exogenously expressed PDK 1 was also tyrosine phosphorylated in response to NGF treatment of 293T expressing TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the present study , we examined the effect of nerve growth factor ( NGF ) on IFN gamma induced TrkA protein to clarify the relationship between TrkA and cell differentiation of NB . ^^^ Tyrosine phosphorylation pattern after 5 min of NGF stimulation was also examined in immunoblot analysis with anti gp 140 ( trkA ) antibody and antiphospho tyrosine antibody . ^^^ Although the degree of morphological differentiation did not increase in proportion to the TrkA expression induced by IFN gamma , continuous loading of both IFN gamma and NGF caused marked morphological differentiation in a cultured KP N RT cell line and SK rib cells during 10 days . ^^^ Moreover , 5 min of NGF stimulation after IFN gamma treatment caused the phosphorylation of TrkA protein and downstream proteins . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Actions of the NGF family of neurotrophins are not only dictated by ras activation through the Trk family of receptor tyrosine kinases , but also a survival pathway defined by phosphatidylinositol 3 kinase activity ( Yao and Cooper , 1995 ) , which gives rise to phosphoinositide intermediates that activate the serine / threonine kinase Akt / PKB ( Dudek et al . , 1997 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
RESULTS : In contrast to previously studied normal retinal precursor cells , Y 79 cells not only express nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , neurotrophin 3 ( NT 3 ) , and p 75 , but also the corresponding high affinity receptors TrkA , TrkB , and TrkC . ^^^ However , despite the high level of TrkA expression in differentiated cells , the addition of NGF had no effect on their survival . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF stimulation of erk phosphorylation is impaired by a point mutation in the transmembrane domain of trkA receptor . ^^^ The nerve growth factor ( NGF ) trkA receptor is a transmembrane glycoprotein composed of a large extracellular ligand binding region connected to the cytoplasmic tyrosine kinase region by a single transmembrane domain ( TMD ) . ^^^ NIH 3T3 cells lacking endogenous NGF receptors were stably transfected with a pRc / CMV vector carrying either wild type ( trkA ) or mutated ( V432E ) receptors . ^^^ Stable transfectants were shown , using 125I NGF binding and Western blot analysis , to express the trkA recombinant receptors . ^^^ Although the level of basal trkA receptor tyrosine phosphorylation was higher in the mutant than in the wild type , NGF stimulation of WT 11 and V432E transfectants resulted in a rapid increase in receptor tyrosine phosphorylation and of its intracellular adaptor protein SHC . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We first investigated the immunoreactivity of TrkA , which is a high affinity receptor of nerve growth factor ( NGF ) , in the periodontal ligament of rats . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Retinoic acid potentiated the protective effect of NGF against staurosporine induced apoptosis in cultured chick neurons by increasing the trkA protein expression . ^^^ TrkA protein expression in chick neurons was markedly reduced by staurosporine , but was found to be increased in the presence of RA and NGF compared with the treatment with staurosporine alone . ^^^ The antiapoptotic effect caused by RA and NGF was abolished by the tyrosine kinase inhibitor K 252a , as well as by anti trkA antibodies and anti NGF antibodies suggesting that the increase in trkA protein expression contributed to its mechanism of action . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Recently it has been shown that p 53 can also bind to trk A tyrosine kinase which is the receptor for nerve growth factor ( NGF ) . ^^^ Endogenous c abl was detected when the trk A and p 53 complex was immunoprecipitated from lysates of NGF stimulated NIH3T3 cells expressing trk A or NIH3T3 cells expressing trk A and a temperature sensitive p 53 ( val 135 ) . ^^^ Endogenous c abl and trk A association was observed in NGF stimulated p 53 negative fibroblasts transfected with trk A alone ; suggesting that c abl can independently bind to trk A in the absence of p 53 . ^^^ Interestingly , association between endogenous p 53 and trk A was not detected in NGF stimulated abl negative fibroblasts transfected with trk A or when these cells were exposed to gamma radiation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA codes for the high affinity receptor of NGF , a neurotrophin known to promote differentiation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Long term microglial and astroglial activation in the hippocampus of trimethyltin intoxicated rat : stimulation of NGF and TrkA immunoreactivities in astroglia but not in microglia . ^^^ To assess the trophic response of glial cells ( NGF and TrkA expression ) , single or double staining experiments were performed . ^^^ The main findings of our study were as follows . ( 1 ) A protracted activation of microglia ( at least up to 2 months posttreatment ) . ( 2 ) A long lasting expression of GFAP immunoreactivity ( at least up to 6 months posttreatment ) and a steady increase in GFAP content ( at least up to 2 months posttreatment ) . ( 3 ) The appearance of enormously enlarged , round shape astrocytes exclusively localized to CA 1 and observed 2 months posttreatment . ( 4 ) The stimulation of NGF and TrkA expression in reactive astrocytes . ( 5 ) The strongest activation of micro and astroglia coincided with the most prominent neurodegeneration in the hippocampus , i . e . , in CA4 / CA3c and CA 1 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Cellular responses to NGF are facilitated by two receptors called trk A and p 75 neurotrophin receptor ( p75NTR ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The tyrosine receptor kinases , trkA and trkC , are the cognate receptors for NGF and NT 3 , respectively . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Previous work indicating that nerve growth factor ( NGF ) protein loops 2 and 4 interact with TrkA receptors raise the possibility that small molecule mimetics corresponding to TrkA interacting domains that have NGF agonist activity can be developed . ^^^ We applied our previously developed strategy of dimeric peptidomimetics to address the hypothesis that loop 4 small molecule dimeric mimetics would activate TrkA related signal transduction and mimic NGF neurotrophic effects in a structure specific manner . ^^^ Activity was blocked by the TrkA inhibitors K252a and AG 879 but not by NGF p 75 receptor blocking antibody . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) binds to two neurotrophin receptors : p 75 ( NTR ) and p 140 ( Trk ) ( TrkA ) . ^^^ NGF ligand alters NGF signaling via p 75 ( NTR ) and trkA . ^^^ TrkA homodimers and heteromers of TrkA and p 75 ( NTR ) promote cell survival whereas homodimers of p 75 ( NTR ) mediate apoptosis upon binding of NGF . ^^^ The interaction between receptor and NGF can be inhibited either on the level of the ligand by altering NGF conformation so that NGF is no longer recognized by the receptor or on the level of the receptor by blocking the binding site of p 75 ( NTR ) or TrkA . ^^^ The effect of altering NGF conformation on NGF signaling was investigated in two neuron like cell lines : in human SK N MC cells that express only p 75 ( NTR ) and in rat PC 12 cells that express both p 75 ( NTR ) and TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) and its signal transducing receptor TrkA are expressed in the thymus . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Cell surface Trk receptors mediate NGF induced survival while internalized receptors regulate NGF induced differentiation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF high affinity receptor trk a was expressed continuously in the cells as visualized by Western blotting . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The nerve growth factor ( NGF ) receptors p75LNGR and TrkA are expressed by thymic epithelial cells . ^^^ Presumably , the NGF TrkA system is involved in the paracrine communication between thymic epithelial cells and thymocytes , whereas the functional role of p75LNGR is still unknown . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Such increases may , at least in part , be due to a decreased expression of the NGF high affinity receptor trkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The extracellular region of the nerve growth factor ( NGF ) receptor , TrkA , contains two immunoglobulin ( Ig ) like domains that are required for specific ligand binding . ^^^ Most of these TrkA variants did not bind NGF , and their expression in PC12nnr5 cells , which lack endogenous TrkA , promoted ligand independent neurite outgrowth . ^^^ Our data suggest that spontaneous dimerization of TrkA occurs when the structure of the Ig like domains is altered , implying that the intact domains inhibit receptor dimerization in the absence of NGF . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In this study , we show that triggering of the high affinity NGF receptor TrkA with agonists protects monocytes from apoptosis induced by gliotoxin or UVB radiation . ^^^ In addition , during in vitro monocyte to dendritic cell differentiation TrkA expression is progressively lost , suggesting that NGF selectively affects monocyte but not dendritic cell survival . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF stimulation of grafts increased the message for NGF receptors p 75 and trkA in the chromaffin transplants . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The anabolic or protective actions of estrogen on the neuronal cells are mediated by the modulation of intracellular factors such as insulin like growth factor ( IGF 1 ) , tyrosine kinase A ( Trk A ) , nerve growth factors ( NGF ) etc . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Twenty four hours after stretch , the expression of BDNF , NGF , and TrkA was significantly increased , whereas that of bcl 2 , CREB , and GAD 65 was significantly decreased ( MANOVA followed by ANOVA , p < 0 . 05 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Whereas the TrkA ligand nerve growth factor ( NGF ) has long been known to regulate both the survival and the expression of noradrenergic traits in sympathetic neurons , the role of TrkC and of its ligand neurotrophin 3 ( NT 3 ) has remained unclear . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Six MAbs , which recognize distinct or partially overlapping regions of hNGF , were evaluated for their ability to block the binding of hNGF to the TrkA and p 75 NGF receptors in various in vitro assays , which included blocking of TrkA autophosphorylation and blocking of NGF dependent survival of dorsal root ganglion sensory neurons . ^^^ These results are consistent with recently proposed models of binding regions involved in NGF TrkA and NGF p 75 interactions generated through mutagenic analysis and structure determination of the NGF TrkA complex . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
At least four of the five known neurotrophins , including nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , neurotrophin 3 ( NT 3 ) , and neurotrophin 4 ( NT 4 ) , and their receptors ( p 75 NTR , trkA , trkB and trkC ) are present in the developing ovary . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The mRNAs for NGF , BDNF with exon 4 , NT 3 , p75NTR , and all Trk members were detected in the LN untreated liver . ^^^ LN treatment resulted in increases in the levels of NGF , BDNF with exon 4 , NT 3 , p75NTR , and TrkA mRNAs and further led to expression of BDNF mRNA with exon 3 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) and related neurotrophins influence neuronal survival and differentiation via interactions with the trk family of receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have recently reported that retinoic acid ( RA ) induced the expression of trkA , the high affinity receptor for nerve growth factor ( NGF ) , in human chronic myelogenous leukemia K 562 cells . ^^^ In this paper , we examined the ability of several other differentiation inducers to regulate the expression of trkA and NGF in K 562 cells . ^^^ Furthermore , activation of the up regulated trkA receptor by exogenous NGF potentiated the megakaryocytic differentiation of K 562 cells induced by NaBut and PMA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Moreover , combined deep etching and immunogold techniques revealed the presence of the NGF receptor TrkA in the caveolae of PC 12 cells . ^^^ These data together with the cofractionation of Shc , Ras , caveolin , and TrkA in the caveolae fraction supported a role for these plasma membrane microdomains in NGF signaling . ^^^ In contrast , pretreatment of PC 12 cells with these drugs inhibited the NGF but not the epidermal growth factor induced MAPK phosphorylation without affecting the TrkA autophosphorylation . ^^^ Taken together , our results demonstrate the presence of caveolae in PC 12 cells , which contain the high affinity NGF receptor TrkA , and the specific involvement of these cholesterol enriched plasma membrane microdomains in the propagation of the NGF induced signal . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NRAGE blocks the physical association of p75NTR with TrkA , and , conversely , TrkA overexpression eliminates NRAGE mediated NGF dependent death , indicating that interactions of NRAGE or TrkA with p75NTR are functionally and physically exclusive . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Intracelluar dynamics of a high affinity NGF receptor TrkA in PC 12 cell . ^^^ A high affinity nerve growth factor ( NGF ) receptor , tropomyosin receptor kinase ( TrkA ) , is visualized by expression of TrkA conjugated with cyan fluorescent protein ( CFP ) in PC 12 cells . ^^^ NGF induced differentiation of PC 12 cells transfected with TrkA CFP normally as wild cells without transfection and the expression of TrkA was observed on the entire cell membrane which surrounds the cell body , axons and growth cones . ^^^ Therefore , it is suggested that the PC 12 cell transfected with fluorescent protein conjugated TrkA is a useful model for studying the signal transduction of NGF . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF signals through TrkA to increase clathrin at the plasma membrane and enhance clathrin mediated membrane trafficking . ^^^ Suggesting that clathrin coated membranes serve as one source of signaling endosomes , in earlier studies we showed that nerve growth factor ( NGF ) treatment increased clathrin at the plasma membrane and resulted in colocalization of clathrin with TrkA , the receptor tyrosine kinase for NGF . ^^^ Strikingly , however , we also noted that most clathrin puncta at the surface of NGF treated cells did not colocalize with TrkA , raising the possibility that NGF induces a general increase in clathrin coated membrane formation . ^^^ Significantly , NGF signaled through TrkA to induce an increase in clathrin mediated membrane trafficking , as revealed in the increased endocytosis of transferrin . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Observations on AD brain indicate increases in NGF and decreases in BDNF in surviving neurons of hippocampus and certain neocortical regions and decreases in TrkA in cortex and nucleus basalis . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Together with previous data , this suggests that the alteration of trk gene expression could contribute to a decrease in NGF binding sites and its protective effects on cholinergic neurons of AD patients . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Activation of TrkA by its ligand nerve growth factor ( NGF ) initiates a cascade of signaling events and promotes neuronal differentiation in vitro . ^^^ Introduction of TrkA and TrkB restored responsiveness of SH SY5Y cells to the ligands NGF and BDNF , respectively , and resulted in morphological differentiation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The C D loop in nerve growth factor ( NGF ) is involved in binding to the NGF receptor , TrkA . ^^^ We have previously shown that a small cyclic peptide derived from the C D loop of NGF binds to the TrkA receptor by mimicking the structure of this loop . ^^^ The variety of active loop conformations suggests that the mimetics ( and NGF ) accommodate the binding site on TrkA by an ' induced fit ' mechanism . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Current study sought to examine changes of the nerve growth factor ( NGF ) receptor TrkA in DRG and spinal cord after a spinal nerve transection by an immunohistochemical technique and to investigate effects of NGF on the expression of TrkA protein in the same animal model . ^^^ Exogenous NGF delivered to DRG for 2 weeks partially reversed the reduction of TrkA expression as well as atrophy of TrkA immunoreactive neurons . ^^^ Our data show that unilateral peripheral nerve injury results in dynamic downregulation of TrkA in sensory neurons in bilateral DRG and spinal cord , and that TrkA expression in sensory neurons is partially regulated by target derived NGF . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The short and long term effects of nerve growth factor ( NGF ) were studied on fibroblast cell lines stably expressing both TrkA and either wild type p 75 or a mutant that lacks the palmitoylation site of p 75 . ^^^ The lack of palmitoylation had no effect on the ability of p 75 to enhance the short term NGF induced tyrosine phosphorylation of TrkA over a wide range of NGF concentrations . ^^^ Long term treatment of the cell lines with NGF led to loss of cell adhesion to the culture dishes that increased with increasing concentrations of NGF and increased expression of TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To mediate these actions , NGF binds to the TrkA receptor to trigger intracellular signaling cascades . ^^^ We show that PI 3 K is required for TrkA internalization and participates in NGF signaling to ERKs via distinct actions on the small G proteins Ras and Rap 1 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the present study , the changes in expression of the neurotrophins ( NGF , BDNF , and NT 3 ) and their cognate receptors ( i . e . , trk and p75NTR ) during the progression of normal prostatic epithelial cells to malignancy were documented . ^^^ METHODS : Immmunocytochemistry , RT PCR , and ELISA assays were used to characterize the changes in the neurotrophin ligands ( i . e . , NGF , BDNF , and NT 3 ) and their cognate high affinity ( i . e . , trk A , B , and C ) and low affinity neurotrophin ( i . e . , p 75 NTR ) receptors in normal vs . malignant human prostatic tissues . ^^^ In contrast , malignant prostate epithelial cells directly secrete a series of neurotrophins ( i . e . , NGF , BDNF , and / or NT 3 ) and express at least one if not more of the trk receptor proteins ( i . e . , trk A , B , and / or C ) , while no longer expressing the p75NTR receptors . ^^^ While the NGF / trkA / p75 NTR axis is present in the normal prostate , normal prostatic epithelial cells do not depend on this axis for their survival . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To elucidate the events leading to this drastic change , MTSV 1 7 cells and its subclone HB 2 ( which shows a more strictly epithelial phenotype ) were transfected with the hybrid trk neu receptor consisting of the extracellular domain of the trkA nerve growth factor ( NGF ) receptor and the transmembrane and cytoplasmic domains of c erbB 2 ( neu ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These cholinergic septal afferents are capable of responding to target derived NGF because they possess trkA and p 75 ( NTR ) , the two transmembrane receptors that bind NGF and activate ligand mediated intracellular signaling . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
METHODS : Immunocytochemistry and Western blot analyses were performed using primary antibodies raised against NTs ( nerve growth factor [ NGF ] , brain derived neurotrophic factor [ BDNF ] , NT 3 , and NT 4 / 5 ) and NT receptors ( TrkA , TrkB , TrkC , and p75NTR ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Therefore , a single TrkA effector , PI 3 K , has multiple roles within spatially distinct cellular locales during retrograde NGF signaling . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
RESULTS : All four transfected cell lines demonstrated high TrkA expression and similar activation of the TrkA receptor and of mitogen activated protein kinases as well as induction of immediate early genes in response to nerve growth factor ( NGF ) . ^^^ Introduction of TrkA restored NGF responsiveness of SH SY5Y and NB 69 cells , as demonstrated by morphologic differentiation , growth inhibition , and enhanced survival in serum free medium . ^^^ However , no morphologic , growth , or survival responses to NGF were detected in MYCN amplified CHP 134 and IMR 5 TrkA transfectants . ^^^ CONCLUSIONS : Thus , transfection of TrkA into MYCN amplified NB cell lines only partly restored the TrkA / NGF signaling pathway , suggesting additional inhibitory effects of MYCN overexpression on TrkA signaling . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Interestingly , NGF down regulated the expression levels of WT 1 and EGFR in PC 12 cells , but not in the p 140 ( trk ) deficient variant PC12nnr5 cells or in cells expressing either dominant negative Ras or dominant negative Src . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To determine whether reduced nerve growth factor ( NGF ) and / or its high affinity receptor , trkA , play a role in the pathophysiology of Rett syndrome ( RS ) , we used immunohistochemistry in paraffin embedded human autopsy brain tissue , to quantify NGF and trkA levels within the frontal cortex of 9 RS females and 10 female controls of similar age . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Mature nodose and petrosal ganglia neurons ( placodally derived afferent neurons of the vagal and glossopharyngeal nerves ) contain TrkA and TrkC , and transport specific neurotrophins [ nerve growth factor ( NGF ) , neurotrophin 3 ( NT 3 ) , neurotrophin 4 ( NT 4 ) ] . ^^^ These data , coupled with previous evidence for the presence of TrkA and TrkC mRNA and of the retrograde transport of NGF and NT 3 , suggest important roles for NGF and NT 3 in the maintenance of transmitter phenotype of these mature visceral afferent neurons . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The expression of trk A ( the high affinity receptor for NGF ) was located in Sertoli and interstitial cells at E 16 P5 . ^^^ In summary , observations suggest that NT 3 , NGF , trk A , and trk C are localized to cells critical to seminiferous cord formation and appear to be important regulators of morphological sex determination . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The sIgG ( + ) lymphoblastoid B cell line CESS spontaneously produces a high amount of NGF and expresses both high affinity ( p 140 ( Trk A ) ) and low affinity ( p 75 ( NTR ) ) NGF receptors . ^^^ Blocking NGF signals with neutralizing antibodies or specific Trk A inhibitors induces a rapid phosphorylation of antiapoptotic Bcl 2 protein , followed by caspase activation , and apoptotic death of CESS cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) has been demonstrated to support survival and differentiation of neuroblastoma ( NB ) cells by activation of the TrkA receptor . ^^^ However , additional transfection of TrkA into SY5Y p 75 cells resulted in a significantly reduced rate of apoptosis even in the absence of NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA , the nerve growth factor ( NGF ) tyrosine kinase receptor , is expressed not only in the nervous system , but also in nonneural cells , including discrete cellular subsets of the endocrine and immune system . ^^^ Blockade of either trkA transducing capacity or NGF biological activity inhibited ovulation , suggesting a role for NGF in the ovulatory process of this species . ^^^ Ribonuclease protection assays employing bovine specific cRNA probes demonstrated the presence of the messenger RNAs ( mRNAs ) encoding NGF and its receptors , p 75 NTR and trkA , in the thecal compartment of small , medium , and large antral follicles and showed that trkA mRNA is also expressed in granulosa cells . ^^^ In situ hybridization and immunohistochemical examination of intact ovaries confirmed these cellular sites of NGF and trkA synthesis . ^^^ TrkA mRNA , but not NGF mRNA , was lost within 48 h of placing thecal cells in culture . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We show immunoreactivity to antibodies to nerve growth factor ( NGF ) , brain derived neurotrophin ( BDNF ) , neurotrophin 3 ( NT 3 ) , neurotrophin 4 / 5 ( NT 4 / 5 ) , the low affinity nerve growth factor receptor p 75 and the high affinity tyrosine kinase receptors ( Trk ) B and C in hepatic stellate cells and weak reactivity for BDNF , NT 3 , and NT 4 / 5 in hepatocytes , in cryosections of human and rat liver , in normal and varying pathologic conditions . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These effects required at least 48 hr exposure to the neurotrophin and were specific for trkB , because they were not seen with the trkA or trkC ligands NGF or NT 3 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We hypothesized that the female sex steroid hormones upregulate NGF receptors , trkA and p 75 ( NTR ) , in DRG . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The effect of NGF applied onto the olfactory epithelium is consistent with the immunohistochemical finding that Trk A was present in the dendrites and axon bundles in normal and axotomized ORNs . ^^^ These results suggest that NGF may protect the degenerative changes in mature and immature ORNs following axotomy through the binding to the Trk A receptor located on the surface of the olfactory epithelium . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In neural crest derived sensory ganglia , approximately half of the neuronal population expresses the transmembrane trkA receptor that is required for neuronal binding of target derived nerve growth factor ( NGF ) . ^^^ These same neurons also express the p 75 neurotrophin receptor ( NTR ) that increases the affinity of trkA for NGF . ^^^ In response to elevated levels of NGF protein , transgenic mice with and without p75NTR expression display both increased levels of trkA mRNA expression and a greater density of trigeminal central afferent axons as compared to control mice . ^^^ These data further reveal that an absence of p75NTR function in trigeminal sensory neurons does not diminish their capacity for NGF dependent plasticity , namely trkA mRNA expression and collateral growth of central afferent axons . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
PC 12 and INS 1 cells both express the nerve growth factor ( NGF ) receptors trkA and p75NTR and the epidermal growth factor receptor ( EGF ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) influences differentiation and proliferation of myogenic cells in vitro via TrKA . ^^^ During differentiation , muscle cells also express some neurotrophin receptors , such as the low affinity p 75 neurotrophin receptor , which binds all neurotrophins , and the high affinity tyrosine kinase receptor TrKA , nerve growth factor ( NGF ) transducing receptor . ^^^ As expected , all the three cell types expressed NGF , p 75 and TrKA . ^^^ TrKA was constitutively immunodetected in all the three cell lines , suggesting that these cells may respond to NGF . ^^^ The present data also suggest that these effects of NGF are mediated by TrKA receptors and that a sustained presence of NGF is needed for increase fusion into myotubes . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Adult septohippocampal cholinergic neurons are dependent on trophic support for normal functioning and survival ; these effects are largely mediated by the tyrosine kinase A receptor ( TrkA ) , which binds its ligand , nerve growth factor ( NGF ) , with high affinity . ^^^ The findings that presynaptic profiles contain TrkA immunolabeling in sites of vesicle accumulation suggest that NGF binding to TrkA may influence transmitter release . ^^^ The presence of TrkA immunoreactivity in somata , dendrites , and glia further suggests that cells within the dentate gyrus may take up NGF . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Most studies have focused on the nerve growth factor ( NGF ) / TrkA pathway in peripheral neurons , and little is known regarding the other neurotrophins , particularly neurotrophin 3 ( NT 3 ) / TrkC . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TRK T 1 oncogene is generated by the rearrangement of the NGF receptor TrkA with TPR . ^^^ TRK T 1 oncogene is generated by the rearrangement of the NGF receptor TrkA with TPR . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Gene trap analysis of germ cell signaling to Sertoli cells : NGF TrkA mediated induction of Fra 1 and Fos by post meiotic germ cells . ^^^ The effect of NGF was mediated by the TrkA receptor and the ERK 1 ERK2 kinase kinase pathway . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Furthermore , antisense p75NTR oligonucleotides rescued trkA , B , and C expressing neurons , while NGF and leukemia inhibitory factor targeted primarily the trkA positive neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The TrkA receptor is activated primarily by nerve growth factor ( NGF ) , but it can also be activated by high concentrations of neurotrophin 3 ( NT 3 ) . ^^^ The pan neurotrophin receptor p 75 ( NTR ) strongly inhibits activation of TrkA by NT 3 but not by NGF . ^^^ Application of NGF or NT 3 to oocytes expressing TrkA alone resulted in efflux of ( 45 ) Ca ( 2+ ) by a phospholipase C gamma dependent pathway . ^^^ Coexpression of p 75 ( NTR ) with TrkA inhibited ( 45 ) Ca ( 2+ ) efflux in response to NT 3 but not NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In our second experiment , we blocked effects that NGF has at 1 week after training by infusing antisense TrkA phosphorothioate DNA oligonucleotide . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
PS 1 protein accumulation was dose responsive to NGF and required the presence of the TrkA NGF receptor tyrosine kinase . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Human TRKA ( NTRK 1 ) encodes the receptor tyrosine kinases ( RTKs ) for nerve growth factor ( NGF ) and is the gene responsible for congenital insensitivity to pain with anhidrosis ( CIPA ) , an autosomal recessive disorder characterized by a lack of pain sensation and anhidrosis . ^^^ Here we have introduced the corresponding mutations into the TRKA cDNA and examined NGF stimulated autophosphorylation . ^^^ We find that wild type TRKA precursor proteins in a neuronal and a non neuronal cell line were differentially processed and phosphorylated in an NGF dependent and independent manner , respectively . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) regulates the nociceptive properties including sensitivity to capsaicin of a subset of dorsal root ganglion neurons , which express the high affinity NGF receptor , trkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The amount and distribution of the NGF receptors p 75 ( NTR ) and TrkA were measured in the dorsal horn and dorsal root ganglia ( DRG ) of animals subjected to Freund ' s adjuvant induced arthritis ( AIA ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immunohistochemical localization of NGF receptors ( trkA and p 75 ) showed that virtually all noradrenergic and a minority of cholinergic pelvic neurons expressed both receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The common neurotrophin receptor p 75 ( NTR ) ( low affinity nerve growth factor receptor ) participates in the high affinity binding with the TrkA nerve growth factor ( NGF ) receptor , may mediate apoptosis , and may signal independently in a cell specific manner . ^^^ The potential of p 75 ( NTR ) to signal independently of TrkA was investigated with an NGF mutant protein ( NGFdelta9 / 13 ) that binds poorly to TrkA ( Woo et al . [ 1995 ] J . ^^^ The NGFdelta9 / 13 mutant does not activate TrkA autophosphorylation and fails to stimulate the normal NGF induced growth arrest , demonstrating that TrkA activation is required to arrest PC 12 cells at the NGF activated G1 / S cell cycle checkpoint . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The peroxynitrite generator 3 morpholinosydnonmine ( SIN 1 ) was used to examine the effects of peroxynitrite generation on nerve growth factor ( NGF ) / TrkA signaling in PC 12 pheochromocytoma cells that express a cholinergic phenotype . ^^^ Pretreatment with SIN 1 also resulted in a decrease in the NGF induced phosphorylation of TrkA protein . ^^^ These data suggest that SIN 1 treatment inhibits NGF signaling by inactivating TrkA receptors through the formation of nitrotyrosine residues on the receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Using a newly developed FACS single cell deposition technique , we evaluated the capacity of single EGF stimulated neurosphere cells to respond to the ligands for Trk A and B , nerve growth factor ( NGF ) , and brain derived neurotrophin factor ( BDNF ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TRK 1 cells cease to proliferate and extend long processes in response to NGF , while E 25 cells continue to proliferate in the presence of NGF . ^^^ As judged by NADPH diaphorase staining , nitric oxide synthase ( NOS ) activity is increased in TRK 1 cells upon exposure to NGF . ^^^ Immunocytochemistry shows that levels of the brain NOS ( bNOS ) isoform are increased in TRK 1 , but not E 25 , cells exposed to NGF . ^^^ Furthermore , Western blots show that NGF elevated cyclin dependent kinase inhibitor , p 21 ( WAF 1 ) , in TRK 1 cells only . ^^^ We have examined nerve growth factor ( NGF ) triggered signaling in two NIH3T3 cell lines exogenously expressing the NGF receptor , TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF interacts with high affinity binding sites , termed trk A receptors , located on the cell membranes of responsive neurons . ^^^ If NGF induces wound repair and / or nociceptive responses in tooth pulp , then changes in expression of NGF receptors ( trk A receptors ) in response to dentin injury would be expected . ^^^ To characterize the role of trk A receptors in mediating NGF induced signals to sensory neurons , trigeminal ganglia from adult male rats were examined for changes in expression of trk A as a function of time after injury to maxillary molar dentin . ^^^ Thus our results suggest that NGF may be mediating repair and pain responses by the sustained upregulation of its cell surface receptor , trk A , in neurons of the trigeminal ganglia . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Our starting point for the work was that NGF and its receptor TrkA are expressed in a partially overlapping pattern in the inner nuclear layer of the developing retina . ^^^ Our results show that TrkA and NGF expressing cells are postmitotic . ^^^ We show that these horizontal cells co express TrkA and NGF , unlike a subpopulation of amacrine cells that only expresses TrkA . ^^^ Intraocular injections of NGF protein rescued the dying amacrine cells and injection of antisense oligonucleotides for NGF that block its synthesis , caused death among the TrkA expressing horizontal cells , which normally would survive . ^^^ Our results suggest that NGF supports the survival of TrkA expressing avian horizontal cells in an autocrine mode of action in the retina of E 10 E12 chicks . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Several lines of evidence implicate nerve growth factor ( NGF ) signaling through its receptors ( TrkA and p 75 ( NGFR ) ) as a potential source of communication between the two systems . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To study the role of nerve growth factor ( NGF ) in local inflammation , we investigated the expression of NGF and its receptors , trkA and p 75 , in the ankle joints of adjuvant induced arthritic rats . ^^^ Infiltrated mononuclear cells revealed a positive immunoreactivity for NGF and trkA ; they were also positive for immunostaining for W3 / 25 and ED 1 , which mainly stain T cells and macrophages , respectively . ^^^ Changes in the ratios of NGF positive cells to mononuclear cells showed a relatively similar pattern for trkA positive cells , which peaked at weeks 2 to 3 after the adjuvant injection . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These unglycosylated Trk can hardly respond to its ligand , NGF . ^^^ These data strongly suggest that spatial segregation of GM 1 from the Trk protein by the inhibition of the glycosylation of Trk might be an important molecular mechanism for the unresponsiveness to NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Expression of exogenous trkA in neuroblastoma cells restores their ability to differentiate in response to nerve growth factor ( NGF ) . ^^^ Although induced Erk 1 / 2 and Akt / PKB phosphorylation was stronger in NT 3 stimulated SH Y5Y / trkC cells , activation of the immediate early genes tested was more prominent in NGF treated SH SY5Y / trkA cells . ^^^ The concentrations of norepinephrine , the major sympathetic neurotransmitter , and growth cone located synaptophysin , a neurosecretory granule protein , were increased in NGF treated SH SY5Y / trkA but not in NT 3 treated SH SY5Y / trkC cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We investigated NGF and its receptors ( TrkA and p 75 ) in pancreatic cancer cells ( PANC 1 , MIA PaCa 2 , CAPAN 1 , ASPC 1 , and T3M4 ) by reverse transcription PCR , Western blot analysis , NGF ELISA , and growth assays . ^^^ NGF led to the phosphorylation of TrkA , mitogen activated protein kinase ( MAPK ) , and p 38 MAPK but not stress activated protein kinase / c Jun NH 2 terminal kinase in PANC 1 and MIA PaCa 2 cells . ^^^ In conclusion , the effects of NGF on pancreatic cancer cell growth are dependent on the expression levels and the balance of its TrkA and p 75 receptors . ^^^ NGF induced pancreatic cancer cell growth seems to be mediated through the phosphorylation of TrkA and subsequently via MAPK . ^^^ These results point to a previously unknown autocrine / paracrine pathway in pancreatic cancer , suggesting that NGF TrkA interactions are important factors influencing cell growth and spread in this malignancy . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In general , it appears that some receptor systems have evolved to enhance endosomal signaling , as is the case for TrkA and NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Studies using in situ hybridization histochemistry showed that axotomy of the cervical vagus nerve resulted in increased expression of mRNAs for nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , and neurotrophin 3 ( NT 3 ) , and for TrkA , TrkB , and TrkC receptors in non neuronal cells at both the proximal and distal segments of the transected cervical vagus nerve . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) binding to both p 75 and TrkA neurotrophin receptors activates the transcription factor nuclear factor kappaB ( NF kappaB ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA , the receptor for nerve growth factor ( NGF ) , is tightly regulated during embryonic development and is essential for the survival and differentiation of neural crest derived sensory and sympathetic neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF initiates the majority of its neurotrophic effects by promoting the activation of the tyrosine kinase receptor TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The less effectivity of NGF via TrkA , which was immunocytochemically shown in human OL , and of TPA via the protein kinase C ( PKC ) pathway , may have its common focus on the mitogen activated protein kinase ( MAPK ) cascade . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Cotreatment of NGF ( 20 ng / mL ) with K252a ( 200 nM ) abolished increases in ChAT activity and prevented enhancement of K ( + ) stimulated ACh release beyond the level associated with K252a , suggesting the involvement of TrkA receptor signaling . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Light and electron microscope immunohistochemistry was used to assess the distribution and identity of NGF , p 75 , and trk expressing elements . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
When TrkA is introduced into the cells , NGF also induces differentiation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Three neurotrophins , nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) and neurotrophin 4 / 5 ( NT 4 / 5 ) , induced tyrosine phosphorylation of panTRK , and BDNF and NT 4 / 5 induced tyrosine phosphorylation of TRK B . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) mediates a variety of nerve cell actions through receptor tyrosine kinase TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Through alterations in gene expression , NGF is important in maintaining and regulating the phenotype of neurons that express the high affinity receptor , trkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Oncogenes relevant to the thyroid carcinogenesis are : mutated TSHR and gsp ( constitutive activation of cAMP ) ; TRK ( receptor for NGF ) ; RET / PTC ( phosphorylation of tyrosine kinase receptor ) an isoform of this oncogene is induced by radiation : ras ( it encodes Gs proteins transducing mitogenic signals ) ; and c MET ( receptor for hepatocyte growth factor ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In response to nerve growth factor ( NGF ) , Trk A activation inhibited p 75 ( NTR ) dependent sphingomyelin ( SM ) hydrolysis . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Overexpression of SH 2 B enhances both the magnitude and duration of TrkA autophosphorylation following exposure of PC 12 cells to NGF , and this effect requires the amino terminal multimerization motif . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In concordance with results with Trk mutants , drug mediated inhibition of PLC gamma activity also blocks PN 1 induction by NGF . ^^^ Mutation of TrkA at key autophosphorylation sites indicates an essential role for the phospholipase C gamma ( PLC gamma ) binding site , but not the Shc binding site , for NGF triggered induction of PN 1 . ^^^ Examination of the kinetics of TrkA autophosphorylation indicates that triggered signaling does not result from sustained activation and autophosphorylation of the TrkA receptor kinase , whose phosphorylation state declines rapidly after NGF removal . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
However , the differences between these two factors include the sequence regions determining the specificity of NGF interaction with Trk A or p 75 receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We analyzed immunohistochemical expression of neurotrophins ( NGF , BDNF , NT 3 ) and the cognate receptors , Trk tyrosine kinase receptor family ( TrkA , B , C ) and p75NGFR in 28 surgically resected PDAC specimens . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The effect of NGF appeared to be mediated by its trkA receptors ( trkA ( NGFR ) ) , as suggested by the potent inhibition of both MCF 7 cell proliferation and trkA ( NGFR ) phosphorylation occurring upon treatment of cultures with the selective trkA ( NGFR ) inhibitor K252a . ^^^ Surprisingly , the antiestrogen drug tamoxifen ( TAM ) inhibited NGF induced MCF 7 cell proliferation and trkA ( NGFR ) phosphorylation in a concentration related fashion . ^^^ The effect of TAM seemed to be estrogen receptor independent , because the pure estrogen receptor antagonist ICI 182 . 780 was unable to block NGF induced trkA ( NGFR ) phosphorylation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The TrkA NGF receptor extracellular region contains three leucine repeats flanked by cysteine clusters and two immunoglobulin like domains that are required for specific ligand binding . ^^^ Here we report a specific mutation that increases the binding affinity of the TrkA receptor for NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Pregnancy induced denervation of the human uterine artery correlates with local decrease of NGF and TrkA . ^^^ Whether a decrease of NGF and / or its signal transducing receptor TrkA are involved in this physiological denervation of the uterine artery during pregnancy has not been analyzed . ^^^ On the other hand , the tissular levels of NGF , the density of TrkA , and the immunostaining for both NGF and TrkA , were significantly reduced in uterine arteries from pregnant patients . ^^^ These results strongly suggest that the physiological denervation occurring in the uterine artery during pregnancy is related to a decrease in the availability of NGF by nerve fibers , and to the impossibility to mediate its effect due to a remarkable decrease in the signal transducing TrkA receptor . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Both the NT receptor p 75 ( NTR ) and the NGF tyrosine kinase receptor trkA were found to be expressed in the ovaries of infantile normal mice and mice carrying a null mutation of the NGF gene . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Neurotrophins interact with two types of cell surface receptors : a low affinity receptor ( p 75 NGF R ) and a high affinity tyrosine kinase receptor belonging to the trk proto oncogene family , both expressed in the nervous system and in certain non neuronal tissues . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
K252a ( 10 100 nm ) , BAPTA AM ( 25 microm ) , and Cd ( 2+ ) ( 200 microm ) prevented NGF enhancement of ACh release , suggesting the involvement of TrkA receptors , Ca ( 2+ ) , and voltage gated Ca ( 2+ ) channels , respectively . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The neurotrophins nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , and neurotrophin 3 ( NT 3 ) promote neuronal survival via tyrosine kinase ( Trk ) receptors , whereas NGF and BDNF can also induce apoptosis in developing neurons through p 75 ( NTR ) receptors in the absence of their respective Trk receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the present work , specific activation of protein kinase C ( PKC ) isoforms and of intracellular signal transduction pathways , which include nerve growth factor ( NGF ) receptor trkA , phospholipase C ( PLC ) gamma 1 and extracellular regulated kinases ( ERKs ) 1 and 2 , by the recombinant C terminal portion of the TeTx heavy chain ( H ( C ) TeTx ) is reported . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Both skin and lung fibroblasts were found to produce NGF and to express tyrosine kinase receptor ( trkA ) under basal conditions , whereas the low affinity p 75 receptor was expressed only after prolonged NGF exposure . ^^^ Fibrotic human lung or skin tissues displayed immunoreactivity for NGF , trkA , and p 75 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The growth promoting effects of NGF and NT 3 are almost entirely blocked by K252a , demonstrating that these effects are mediated via activation of Trk receptors , which therefore appear to remain crucial to plasticity of adult neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have shown previously that estrogen increases mRNA and protein expression of the nerve growth factor ( NGF ) specific tyrosine kinase receptor , trkA , while decreasing expression of the universal neurotrophin receptor p 75 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Breast cancer cell lines ( MCF 7 , T 47 D , BT 20 , and MDA MB 231 ) were found to express both types of NGF receptors : p 140 ( trkA ) and p 75 ( NTR ) . ^^^ The mitogenic effect of NGF on breast cancer cells required the tyrosine kinase activity of p 140 ( trkA ) as well as the mitogen activated protein kinase ( MAPK ) cascade , but was independent of p 75 ( NTR ) . ^^^ In contrast , the anti apoptotic effect of NGF ( studied using the ceramide analogue C 2 ) required p 75 ( NTR ) as well as the activation of the transcription factor NF kB , but neither p 140 ( trkA ) nor MAPK was necessary . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Given the known role of neurotrophin signaling in neuronal maturation and apoptosis , we analyzed immunohistochemically the distribution of neurotrophin receptors TrkA and TrkC and their primary ligands NGF and NT 3 in 14 nodular medulloblastomas . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Macrophages expressed NGF and the NGF receptors TrkA and p 75 . ^^^ The induction of TNF alpha production by NGF was blocked by K252a , an inhibitor of the TrkA receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Moreover , GRK 2 is constitutively bound with the Trk A receptor , whereas NGF stimulates the pertussis toxin sensitive binding of beta arrestin 1 to the TrkA receptor GRK 2 complex . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In contrast , no significant changes in the expression of the NGF receptor TrkA were noted under the same conditions . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Bradykinin and nerve growth factor ( NGF ) are two such pro algesic agents that activate G protein coupled ( BK 2 ) and tyrosine kinase ( TrkA ) receptors , respectively , to stimulate phospholipase C ( PLC ) signalling pathways in primary afferent neurons . ^^^ Moreover , recruitment of PLC gamma to TrkA is essential for NGF mediated potentiation of channel activity , and biochemical studies suggest that VR 1 associates with this complex . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Dorsal root ganglion ( DRG ) neurons that mediate nociception express the high affinity NGF receptor ( trkA ) gene and the preprotachykinin ( PPT ) gene . ^^^ These data coupled with our earlier observations of the effect of short term estrogen replacement on DRG trkA mRNA levels , indicate that the regulation of DRG beta PPT mRNA levels by estrogen requires target derived NGF . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Almost all BDNF mRNA expressing neurons coexpressed trkA , a high affinity NGF receptor , mRNA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , and neurotrophin 3 ( NT 3 ) are three representative neurotrophins responsible for the differentiation and survival of neurons , and their high affinity receptors are tropomyosin receptor kinase ( TRK ) A , TRKB , and TRKC , respectively . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the present study , we have assayed the expression of NGF receptors ( NGFRs : TrkA and p 75 ) mRNAs in 363 human primary breast cancers , using real time quantitative reverse transcription PCR . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) binds to the TrkA tyrosine kinase and the p 75 neurotrophin receptors . ^^^ C 6 2B glioma cells express the p 75 receptor , but NGF decreases their growth only when TrkA is introduced ( C6trk ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The four mammalian neurotrophins NGF , BDNF , NT 3 and NT 4 each bind and activate one or more of the Trk family of receptor tyrosine kinases . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
PEA enhanced AEA evoked inhibition of the expression of NGF Trk receptors , which underlies the anti proliferative effect of the endocannabinoid on NGF stimulated MCF 7 cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
At E 17 , almost all Na ( 5 ) 1 . 8 expressing neurons also express the high affinity NGF receptor TrkA , and only a small proportion bind to IB 4 , a marker for c ret expressing ( glial derived neurotrophic factor responsive ) neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) interacts with two structurally unrelated receptors , the Trk A receptor tyrosine kinase and p 75 , a tumor necrosis factor receptor family member . ^^^ Surprisingly , extracellular domain mutations of p 75 that abolished NGF binding still generated high affinity binding with Trk A . ^^^ These results indicate that the transmembrane and cytoplasmic domains of Trk A and p 75 are responsible for high affinity site formation and suggest that p 75 alters the conformation of Trk A to generate high affinity NGF binding . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
However , inhibition of endocytosis of NGF by ceramide could not be ascribed to decreased phosphorylation of TrkA . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
RESULTS : Introduction of TrkA restored nerve growth factor ( NGF ) responsiveness of SH SY5Y cells , demonstrated by morphological differentiation and induction of immediate early genes . ^^^ TrkA overexpression leads to growth inhibition in the absence of NGF , whereas NGF treatment results in increased proliferation . ^^^ CONCLUSIONS : Analysis of downstream signaling elements in mutated TrkA receptors indicates that NGF induced differentiation is dependent on TrkA kinase activity , but several redundant pathways seem to be used farther downstream . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF induced the formation of a long lived complex containing C3G / CrkL / Shp2 / Gab2 / TrkA . ^^^ Linking the complex to Rap 1 activation , we coprecipitated activated TrkA and activated MAPK with activated Rap 1 in NGF treated cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This effect is mediated by the activation of the NGF receptor TrkA because the specific inhibitor of Trk phosphorylation K252a also blocks NGF induced increase in insulin secretion , both in the presence and absence of exogenous NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Using immunocytochemistry , we have examined the effect of experimental autoimmune encephalomyelitis ( EAE ) upon the expression of nerve growth factor ( NGF ) and its TrkA and p 75 receptors in astroglia cells of the spinal cord of Lewis rats . ^^^ We have found that , in normal spinal cord , astroglia of white matter expressed both NGF receptors while those in gray matter expressed only TrkA and no astroglia expressed NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To test the hypothesis that metal ion binding to neurotrophins is influenced by pH , the effects of Zn2+ and Cu2+ on NGF conformation , receptor binding and NGF tyrosine kinase ( trkA ) receptor signal transduction were examined under conditions mimicking cerebral acidosis ( pH range 5 . 5 7 . 4 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
On the other hand , two types of NGF receptors have been identified , a low affinity receptor , p75NGFR , and a high affinity receptor , TrkA . ^^^ NGF p75NGFR interaction is known to play an important role in apoptosis , whereas NGF TrkA interaction is responsible for the survival of neural cells . ^^^ We examined the relationship between clinicopathological factors , Ki 67 index , apoptotic index and the immunohistochemical expression of NGF , TrkA and p75NGFR in 71 invasive ductal breast carcinoma ( IDBC ) specimens . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Induction of TrkA mRNA by hCG suggests that high affinity binding of NGF during stages VIIcd 8 in premeiotic cells is under control of the hypothalamic pituitary testicular axis . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In contrast pERK is prominent in a few trkA cells and in satellite glial cells , and is further increased by NGF treatment . tERK and pERK both undergo fast anterograde and retrograde axonal transport , indicated by accumulation at a sciatic nerve ligature , and NGF reduces the level of retrograde pERK transport . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The atRA induced increase in trkA mRNA may play a role in the enhanced survival of neurons cultured in the presence of either NGF or NT 3 , as both neurotrophins have been shown to signal through this receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The monoclonal antibody MNAC 13 is a potent antagonist that prevents the binding of nerve growth factor ( NGF ) to its tyrosine kinase A receptor ( TrkA ) in a variety of systems . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The finding that two proteins , p75NTR and Trk , act as receptors for NGF in neurons generated the discovery of other neurotrophic factors / receptor families and has enhanced our understanding of the development , survival , regeneration , and degeneration of the nervous system . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We compared the gene expression profiles obtained from MED 283 TrkA cells undergoing NGF induced apoptosis to PC 12 cells undergoing NGF induced differentiation . ^^^ An early and specific transcriptional target of NGF in MED 283 TrkA cells was the DNA damage inducible gene gadd 45 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF dramatically up regulated PACAP expression in trkA positive neurons in both intact and injured DRGs , implicating NGF as a positive regulator of PACAP expression in nociceptive neurons . ^^^ Surprisingly , NT 3 modulates PACAP expression in an antagonistic fashion to NGF in intact neurons , an effect most evident in the trkA neurons not expressing trkC . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
No differences were observed for NGF , trk A , NT 3 or NaN / SNS2 immunoreactivity . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Sections of pancreatic cancer and normal pancreatic tissue were examined by immunohistochemistry for the expression of the neurotrophins NGF , BDNF , NT 3 , NT 4 , and their receptors TrkA , TrkB , and TrkC , as well as the low affinity receptor , p75NTR . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
It may modulate the binding of nerve growth factor ( NGF ) to the functional high affinity receptor tyrosine kinase ( trk ) A . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF and its high affinity receptor , TrkA , were immunolocalized using anti NGF and anti TrkA antibodies , respectively . ^^^ The high affinity receptor for NGF , TrkA , was immunolocalized to the infiltrated mast cell membrane . ^^^ In addition , our finding of the presence of the TrkA receptor on the membrane of the infiltrated mast cell in situ brings evidence of the mast cell as a target cell for the growth factor activity of NGF in the airways in asthma . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The mechanism of NGF action is elusive , however , since the presence of its high affinity receptor , trkA , in the cerebral cortex is controversial . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In addition , injection of ovariectomized rats with ovarian hormones led to an increase in levels of two NGF receptors , TrkA and p 75 ( NTR ) , in DRG . ^^^ DRG harvested from rats on specific days of pregnancy , on Day 2 postpartum , and after ovariectomy were subjected to radioimmunoassay , Western blot analysis , and NGF immunoassay to determine levels of CGRP , TrkA and p 75 ( NTR ) , and NGF , respectively . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
METHODS : The expression of NGF and NGF receptors ( gp 140 ( Trk A ) and p 75 ( NTR ) ) were analysed by RT PCR and immunofluorescence . ^^^ RESULTS : We show that NGF and both NGF receptors , gp 140 ( Trk A ) and p 75 ( NTR ) are expressed in beta cells where NGF is produced and secreted in a biologically active form . ^^^ NGF withdrawal induces beta cell transcription / translation independent apoptosis but mediated by gp 140 ( Trk A ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We now report that nerve growth factor ( NGF ) induced activation of the TrkA receptor tyrosine kinase induces MMP 9 expression in both primary cultured rat aortic smooth muscle cells and in a smooth muscle cell line genetically manipulated to express TrkA . ^^^ Activation of the Shc / mitogen activated protein kinase pathway mediates the induction of MMP 9 in response to NGF , as this response is abrogated in cells expressing a mutant TrkA receptor that does not bind Shc and by pretreatment of cells with the MEK 1 inhibitor , U 0126 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The nerve growth factor ( NGF ) dependence of the inflammation induced changes was examined by injecting a synthetic NGF sequestering protein [ tyrosine receptor kinase A Ig 2 ( trkA Ig 2 ) ] with CFA and subsequently into the CFA injection sites . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The expression of NGF ( Trk A ) and bFGF ( flg ) receptors paralleled the switch in trophic requirement . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Involvement of the NGF receptors ( Trka and p75lngfr ) in the development and maintenance of the thymus . ^^^ Nerve growth factor ( NGF ) and its main low ( p75LNGFR ) and high affinity ( TrkA ) receptors have been found in the vertebrate thymus , thus suggesting they are involved in the control of thymic function . ^^^ These results strongly suggest a function of the TrkA NGF system in thymic functions mediated by epithelial cells , as well as a role of TrkA in the development of the murine thymus . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
PURPOSE : The purpose of this study was to analyze the expression of the high and low affinity nerve growth factor ( NGF ) receptors TrkA and p 75 in effusions and in primary and metastatic tumors of serous ovarian carcinoma patients , as well as to evaluate their association with clinicopathological parameters and disease outcome . ^^^ Interestingly , 11 of 16 p 75 positive effusions were also immunoreactive for the antibody against TrkA ( P = 0 . 001 ) , suggesting NGF activation using two signaling pathways . ^^^ The different expression of NGF receptors in effusions may relate to the different microenvironment and growth factor availability in body cavities , as also supported by the infrequent activation of TrkA in effusions . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Because suprachiasmatic neurons do not express trkA , NGF might have exerted its effects either through direct signalling of suprachiasmatic neurons via p 75 ( NTR ) activation or , indirectly , by enhancing the activity of the cholinergic and / or glutamatergic afferents to the suprachiasmatic nucleus , or both . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Furthermore , we demonstrate activation of src by NGF along with formation of a signal complex including the TrkA receptor , src , and PKC iota . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA receptors are both required for uptake of NGF in adult sympathetic neurons : use of a novel fluorescent NGF conjugate . ^^^ Pretreatment of nerve terminals with function blocking antibodies against the low ( p 75 ) and high ( TrkA ) affinity NGF receptors resulted in a large ( 85 93 % ) reduction in numbers of DTR NGF labelled neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
However , the neuritogenesis induced by either the combination of NGF / ionomycin or NGF / dbcAMP was inhibited by the Trk inhibitor , K252a . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
A slight transient increase in the expression of p 75 ( NGFR ) mRNA was observed by 2 to 4 h after retinoid treatment of undifferentiated cells , whereas a larger increase in the expression of both TrkA and p 75 ( NGFR ) mRNA up to threefold the basal level , was observed by 2 to 6 h after retinoid treatment of NGF differentiated cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Populations of NGF dependent neurones differ in their requirement for BAX to undergo apoptosis in the absence of NGF / TrkA signalling in vivo . ^^^ To further examine this assertion in vivo , we have studied two populations of NGF dependent neurones during the period of naturally occurring neuronal death in mice that lack BAX , NGF or the NGF receptor TrkA , alone and in combination . ^^^ In the superior cervical ganglion ( SCG ) , naturally occurring neuronal death and the massive loss of neurones that took place in the absence of NGF or TrkA were completely prevented by elimination of BAX . ^^^ However , in the trigeminal ganglion , naturally occurring neuronal death was only partly abrogated by the elimination of BAX , and although the massive neuronal death that took place in this ganglion in the absence of NGF or TrkA was initially delayed in embryos lacking BAX , this subsequently occurred unabated . ^^^ These results indicate that whereas BAX is required for the death of SCG neurones during normal development and when these neurones are deprived of NGF / TrkA signalling in vivo , the death of trigeminal ganglion neurones occurs independently of BAX when they are deprived of NGF / TrkA signalling . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF induced tyrosine phosphorylation of NGF receptors ( TrkA ) is also consistently suppressed . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Target derived neurotrophins like nerve growth factor ( NGF ) mediate biological effects by binding to and activating Trk neurotrophin receptors at nerve terminals . ^^^ Remarkably , signaling by Trk may differ at the terminal versus the neuronal cell body as a consequence of the retrograde transport mechanism , thereby allowing NGF to not only promote growth locally , but to specifically support survival and gene expression retrogradely . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The target derived neurotrophic factor `` nerve growth factor ' ' ( NGF ) signals through TrkA to promote the survival , differentiation , and maintenance of neurons . ^^^ The `` signaling endosome hypothesis ' ' envisions that NGF TrkA complexes are internalized at the axon terminal and retrogradely transported to the cell body . ^^^ Following NGF treatment , we found that clathrin coated vesicles contained NGF bound to TrkA together with activated signaling proteins of the Ras MAP kinase pathway . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
CONCLUSIONS : Together , the structures of the TrkB d 5 : NT 4 / 5 and TrkA d 5 : NGF complexes confirm a consistent pattern of recognition in Trk receptor : neurotrophin complex formation . ^^^ The contacts formed in the TrkB d 5 : neurotrophin 4 / 5 complex can be divided into a conserved area similar to a region observed in the TrkA d 5 : NGF complex and a second site unique in each ligand receptor pair formed primarily by the ordering of the neurotrophin N terminus . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immunohistochemical analysis of the basal forebrain regions of the same animals demonstrated that the NGF infused into cortex was biologically active , producing an increase in the number of NGF , TrkA , p 75 ( NTR ) , and choline acetyltransferase positive neurons in basal forebrain nuclei in the hemisphere ipsilateral to the NGF minipump compared to the contralateral basal forebrain neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Since NE reduces nerve growth factor ( NGF ) in cultured cardiomyocytes , we proposed to determine whether the loss of noradrenergic transmitters in the failing heart is caused by the NE mediated reduction of NGF or its neurotrophic receptor tyrosine kinase A ( TrKA ) . ^^^ We measured NGF and TrKA proteins by Western blot and immunocytochemistry and measured NGF and TrKA mRNAs by reverse transcription polymerase chain reaction , neuronal catecholaminergic histofluorescence , tyrosine hydroxylase immunostained profiles , and plasma NE . ^^^ Rapid ventricular pacing produced CHF with increased plasma NE , decreased myocardial NGF protein ( 0 . 61 + / 0 . 07 vs . 1 . 04 + / 0 . 04 , P < 0 . 05 ) , TrKA protein ( 0 . 75 + / 0 . 08 vs . 0 . 98 + / 0 . 06 , P < 0 . 05 ) , NGF and TrKA mRNAs and reduced catecholaminergic histofluorescence ( 197 + / 23 vs . 485 + / 43 , P < 0 . 05 ) , and tyrosine hydroxylase profiles ( 360 + / 51 vs . 773 + / 36 , P < 0 . 05 ) . ^^^ Decreases in tissue NGF and TrKA protein were also noted by immunocytochemistry . ^^^ Tissue NGF and TrKA levels correlated closely with the noradrenergic transmitter profiles . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TRKA encodes the receptor tyrosine kinase ( RTK ) for nerve growth factor ( NGF ) and is the gene responsible for CIPA . ^^^ Defects in NGF signal transduction at the TRKA receptor lead to failure to support survival of sympathetic ganglion neurons and nociceptive sensory neurons derived from the neural crest . ^^^ Thirty seven different TRKA mutations , identified in patients in various countries , including nine frameshift , seven nonsense , seven splice , and 14 missense mutations , are distributed in an extracellular domain involved in NGF binding , as well as in the intracellular signal transduction domain . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Neurotrophins , such as NGF , BDNF and NT 3 also utilize receptor tyrosine kinases , namely TrkA , TrkB and TrkC . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The NGF effect was blocked by anti NGF antibody and by K252a , a specific inhibitor for the tyrosine kinase activity of TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Specifically , experiments presented here demonstrate that the presence or absence of p75NTR does not alter Trk activity or NGF and NT 3 mediated downstream survival signaling in primary neurons . ^^^ Developmental sympathetic neuron death is determined by functional interactions between the TrkA / NGF receptor and the p 75 neurotrophin receptor ( p75NTR ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In situ hybridization for trkA mRNA in trigeminal ganglion neurons retrogradely labeled with FluoroGold from the mandibular incisor demonstrated limited expression of the high affinity nerve growth factor ( NGF ) receptor in this presumptive nociceptor population . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Here we show that inactivation of p 75 ( NGFR ) , but not of trkA , resulted in D ( 2 ) receptor loss in responder cells and prevented D ( 2 ) receptor expression induced by NGF in the nonresponder . ^^^ These data indicate that in prolactinoma cells the effect of NGF on D ( 2 ) receptor expression is mediated by p 75 ( NGFR ) in a trkA independent way and that NGF stimulation of p 75 ( NGFR ) activates NF kappaB , which is required for D ( 2 ) gene expression . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
However , the expression of NGF receptors ( NGFRs ) TrkA and p 75 ( NTR ) and the possible sites of NGF action in the visual cortex remain to be elucidated so far . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The receptor for nerve growth factor ( NGF ) comprises a 75 kDa ( NGFRp 75 ) and a tyrosine kinase A ( TrkA ) subunit . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
PURPOSE : To investigate the gene expression of nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , neurotrophin 3 ( NT 3 ) and their high affinity receptors ( TrkA , TrkB and TrkC ) in cultured human Mller cells . ^^^ METHODS : The polymerase chain reaction was performed using specific primers for NGF , BDNF , NT 3 , TrkA , TrkB and TrkC with complementary DNAs as the template , which were generated from poly A+ RNA of cultured human Mller cells . ^^^ RESULTS : We detected the precursor mRNA transcripts for NGF , BDNF , NT 3 , TrkB and TrkC , but not TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the present study , we investigated the biologic effects of trkA neurotrophin receptor activation by nerve growth factor ( NGF ) in a newly established Askin tumor cell line , JK GMS , which constitutively expresses a high level of trkA . ^^^ NGF did not exert significant changes in two different PNET / ES cell lines , CADO ES 1 and RD ES , which did not express detectable levels of trkA . ^^^ The biologic effects mediated by NGF were abrogated by treatment of the cells with K 252a , and the treatment with brain derived neurotrophic factor did not affect the biologic behavior of JK GMS cells , indicating that the effects are trkA specific . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Application of nerve growth factor ( NGF ) covalently cross linked to beads increased the phosphorylation of TrkA and Akt , but not of mitogen activated protein kinase , in cultured rat sympathetic neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
A double cysteine trkA mutant exhibiting reduced NGF binding and delayed Erk signaling . ^^^ The NGF receptor trkA is a tyrosine kinase receptor comprising an extracellular domain with a ligand binding site , a transmembrane spanning domain ( TMD ) , and an intracellular domain composed of a juxtamembrane region ( JMR ) , a tyrosine kinase domain , and a short carboxy terminal tail . ^^^ We hypothesized that the removal of one or both of the cysteines would affect NGF induced signaling of the trkA receptor . ^^^ Here we show that NGF induces rapid receptor autophosphorylation in a wild type , trkA expressing clone ( WT 11 ) , in a single cysteine trkA mutants ( C423T or C436A ) , but lower autophosphorylation activity in a double cysteine trkA mutant ( C423T / C436A ) . ^^^ However , basic fibroblast growth factor ( bFGF ) induced rapid phosphorylation of Erk1 / 2 , and [ 3H ] thymidine incorporation in NIH3T3 , WT 11 , single mutant ( SM ) , and double mutant ( DM ) cells , suggesting that the impaired NGF induced Erk phosphorylation and thymidine incorporation observed in DM cells are due to the double cysteine mutations in the trkA receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The effect of NGF is mediated via TrkA receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF , NT 3 and Trk C mRNAs , but not TrkA mRNA , are upregulated in the paraventricular structures in experimental hydrocephalus . ^^^ DNA oligonucleotide probes for nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , neurotrophin 3 ( NT 3 ) , and trkA , trkB , and C were labeled with [ ( 35 ) S ] dATP using terminal deoxyribonucleotidyl transferase for in situ hybridization . ^^^ The results observed were as follows . ( 1 ) The medial septal and striatal NGF mRNA levels increased with severity in animals . ( 2 ) Hippocampal trkB and BDNF mRNA levels increased with time in animals with moderate ventricular enlargement . ( 3 ) Expression of hippocampal trkB , trkC , and NT 3 mRNA increased in animals with moderate ventricular enlargement , while it apparently decreased in the large ventricular enlargement group reaching normal ranges . ( 4 ) In the corpus callosum there was an apparent increase in NGF , NT 3 and trkC mRNA , but not in trkA , in hydrocephalic animals . ^^^ There were discrepancies in the distribution of NGF and trkA mRNA , and we hypothesize that NGF mRNA in the damaged white matter structure might be due to the reduced availability of other receptors , such as the low affinity NGF receptors . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
OBJECTIVE : To study the effects of transfection of high affinity nerve growth factor receptor gene ( trkA ) on NGF induced differentiation of human neuroblastoma cell line IMR 32 . ^^^ CONCLUSION : Restoration of high affinity NGF receptor ( trkA ) expression in neuroblastoma cells could induce non reversal differentiation . ^^^ The trkA might be the important factor during NGF induced differentiation of neuroblastoma cell . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
High affinity NGF receptor ( TrkA ) levels are decreased in AD brains as compared to age matched control brains . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immunhistochemistry of 10 traumatic human peripheral nerve neuromas and 5 normal digital nerves revealed a high immunoreactivity for the nerve growth factor ( NGF ) receptors p 75 and trkA and the glial cell line derived neurotrophic factor ( GDNF ) receptor GFRalpha 1 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The p 75 low affinity neurotrophin receptor ( p 75 ( LNTR ) ) appears to have various functions that include enhancing nerve growth factor ( NGF ) mediated survival by increasing TrkA ( high affinity NGF receptor ) efficiency , and mediating apoptosis by acting as a ligand regulated pro apoptotic receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This effect is mediated by high affinity TrkA receptor as nerve growth factor ( NGF ) induced the phosphorylation of FKHRL 1 only in TrkA expressing cells and not p 75 expressing cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) belongs by sequence homology to the neurotrophins , a family of proteins binding the same p 75 receptor and closely related members of the Trk family of receptor tyrosine kinases . ^^^ In particular , NGF like and Trk like immunoreactive proteins are both expressed in the nervous system , whereas p 75 like positivity identifies tubular structures associated with dorsal pores that are involved in the earthworm response to mechanical irritation or stress . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Induction by NGF of resistance to apoptosis is primarily thought to be the result of its binding to its high affinity receptor , TrkA . ^^^ The low affinity NGF receptor , p 75 , has long been thought merely to facilitate NGF binding to TrkA . ^^^ However , we have previously shown that the binding of NGF to its low affinity receptor , p 75 , protects neuroblastoma cells that do not express TrkA against apoptosis induced by enediyne chemotherapeutic agents . ^^^ We now show that , in enediyne treated SH SY5Y neuroblastoma transfectants with native levels of p 75 and a low TrkA / p75 ratio ( 1 / 100 ) , the anti apoptotic effect of NGF requires binding to p 75 . ^^^ In contrast , in transfectants with native levels of p 75 and a high TrkA / p75 ratio ( 100 / 100 ) , NGF treatment prevents enediyne induced apoptosis by a mechanism independent of p 75 binding . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Inhibitors of phosphatidylinositol 3 kinase ( LY 294002 ) , mammalian target of rapamycin ( rapamycin ) , and the NGF receptor , TrkA ( K 252a ) , but not of mitogen activated protein kinase ( PD 98059 ) , prevented the recruitment of eEF1A 1 mRNA to polyribosomes . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
METHODS : Expression of nerve growth factor ( NGF ) ; neurotrophins ( NT ) 3 and NT 4 ; brain derived neurotrophic factor ( BDNF ) ; tyrosine kinase transducing receptors TrkA , TrkB , and TrkC ; and a pan NT low affinity receptor ( p 75 ( NTR ) ) was examined by immunostaining in the normal human corneolimbus , HLE grown on intact epithelially denuded AM , and stratified HLE , after subcutaneous implantation in NIH bg nu xid BR mice . ^^^ CONCLUSIONS : The strong expression of TrkA but not p 75 ( NTR ) in the limbal basal epithelial cells in vivo suggests that NGF signaling favors limbal epithelial stem cell survival . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Coexpression of the TrkA receptor with p 75 ( NTR ) further enhances the complexity of nerve growth factor ( NGF ) signaling . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF significantly improved morphological parameters of ChAT and TrkA positive cells in aged rats . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
A central tenet of nerve growth factor ( NGF ) action that is poorly understood is its ability to mediate cytoplasmic signaling , through its receptor TrkA , that is initiated at the nerve terminal and conveyed to the soma . ^^^ We identified an NGF induced protein that we termed Pincher ( pinocytic chaperone ) that mediates endocytosis and trafficking of NGF and its receptor TrkA . ^^^ In PC 12 cells , overexpression of Pincher dramatically stimulated NGF induced endocytosis of TrkA , unexpectedly at sites of clathrin independent macropinocytosis within cell surface ruffles . ^^^ Subsequently , a system of Pincher containing tubules mediated the delivery of NGF / TrkA containing vesicles to cytoplasmic accumulations . ^^^ A dominant inhibitory mutant form of Pincher inhibited the NGF induced endocytosis of TrkA , and selectively blocked TrkA mediated cytoplasmic signaling of erk 5 , but not erk1 / 2 , kinases . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Both Abeta and H ( 2 ) O ( 2 ) induced oxidative stress ( measured by a decrease in cellular glutathione ) , which decreased trk A levels and increased p 75 levels , decreased messenger RNA ( mRNA ) levels of both receptors , and increased nerve growth factor ( NGF ) secretion . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Conjunctival biopsy specimens were used for routine histology , immunohistochemistry ( NGF , trkA , eosinophil cationic protein , and tryptase determination ) , in situ hybridization ( NGF mRNA ) , and determination of fibroblast growth . ^^^ NGF protein , NGF mRNA , and trkA were found to be increased in IJCN biopsy specimens compared with noninflamed compound nevi . ^^^ Some NGF and trkA colocalized with eosinophils and mast cells . ^^^ The data in the current study , showing the presence of increased NG trkA , eosinophils , and mast cells in IJCN and the modulation of eosinophil properties by lesional fibroblasts partly through NGF , suggest a possible association between IJCN and allergic inflammation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The activation of Trk receptors is essential for NGF action , since K252a abolishes the NGF induced potentiation of dopamine release and brain derived neurotrophic factor enhanced ionomycin induced release only in TrkB expressing cells . ^^^ These findings suggest that NGF regulates neurotransmitter release through the activation of TrkA receptors , possibly by increasing the number of secretory vesicles in a readily releasable pool . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have characterized the cell cycle deficit of a novel TrkA receptor mutant ( TrkAS 3 ) that fails to support nerve growth factor ( NGF ) dependent cell cycle arrest and neurite outgrowth . ^^^ Moreover , NGF activated TrkAS 3 receptors do not down regulate cyclin dependent kinase 4 phosphorylation of the retinoblastoma protein , essential for G ( 1 ) arrest , in comparison to NGF activated wild type TrkA . ^^^ Collectively , these data suggest a model in which NGF stimulated TrkA dependent activation of FRS 2 supports neurite outgrowth through a mechanism that likely involves the induction of p 21 ( Waf1 / Cip1 ) expression and the arrest of cells at G ( 1 ) / S . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In addition , the effect of albumin seemed to depend on the activity of the NGF receptor , TrkA , suggesting that the glutamate synthesized and released due to the presence of albumin promotes neuronal survival through the activity of TrkA . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Activation of Akt kinase by NGF was also observed in PC12nnr5 cells and cultured rat hippocampal neurones which both lack significant TrkA expression . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
At the molecular level , NS 1231 enhanced NGF induced signalling events , such as TrkA phosphorylation at the Shc binding site Tyr 490 as well as ERK activation in PC 12 cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Biochemical and molecular analyses of the expression , fate , and kinetics of membrane trafficking of the nerve growth factor ( NGF ) receptor TrkA were performed in PC 12 cells . ^^^ The addition of NGF decreases the half life of cell surface gp 140 ( TrkA ) from 100 to 35 min and leads to enhanced lysosomal degradation of the receptor . ^^^ The process of NGF induced TrkA internalization is clearly affected by interfering with ligand binding to p 75 ( NTR ) . ^^^ Together , these data show that the primary effect of NGF treatment is a p 75 ( NTR ) modulated decrease in TrkA transit time at the cell surface . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This response reached maximal levels as early as 5 min after the initiation of the coincubation and was completely blocked by anti NGF Ab or by an inhibitor for a tyrosine kinase of the trkA NGF receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
METHODS : Expression of NGF , TrkA , and p75NTR was investigated in HCCs developing and regenerating livers , and primary hepatocyte cultures in B6C3F ( 1 ) mice by reverse transcription polymerase chain reaction , Northern blotting , and / or immunohistochemistry . ^^^ TrkA expression and the abundance of nerve fibers in the walls of tumor associated arteries suggest a possible role for NGF in angiogenesis . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) is a neurotrophin required for differentiation , development , and survival of the sympathetic nervous system , with many of its biological effects being mediated via trkA receptors . ^^^ In addition , variant clones PC12nnr5 and PC12EN , lacking trkA receptors , did not respond to NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
However , whether lung cells express neurotrophins and / or their receptors ( TrkA for NGF , TrkB for BDNF and NT 4 / 5 , and TrkC for NT 3 ) has never been systematically investigated . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In this study we used immunohistochemistry to investigate the occurrence and localization both of neurotrophins ( NGF , BDNF and NT 3 like ) and of Trk like proteins ( TrkA , TrkB , TrkC like ) in alevins of Salmo salar and S . trutta . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
PURPOSE : To determine the presence of nerve growth factor ( NGF ) , NGF mRNA , and NGF receptor ( TrkA ) in rabbit ocular tissues , and whether changes occur in NGF and NGF mRNA levels after experimental iridectomy . ^^^ METHODS : Immunohistochemistry for NGF and TrkA and in situ hybridization for NGF mRNA were performed on rabbit cornea , iris , ciliary body , and lens in the basal state . ^^^ RESULTS : Cornea , iris , ciliary body , and lens expressed NGF mRNA , NGF protein , and TrkA in the basal state . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immunohistochemistry with antibodies against NGF , NGF specific tyrosine kinase receptor ( Trk A ) and S 100 protein was performed . ^^^ The specific receptor for NGF ( Trk A ) is expressed in all the nerves that were included in the biopsies . ^^^ The strong expression of the NGF TrkA pathway in deep adenomyotic nodules could explain why this type of lesion infiltrates in richly innervated anatomical sites . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The human TRKA ( NTRKI ) gene located on chromosome 1 ( 1q21 q 22 ) encodes a receptor tyrosine kinase ( RTK ) which is autophosphorylated in response to NGF , thus , activating various pathways of intracellular signal transduction . ^^^ TRKA mutations are distributed in an extracellular domain involved in NGF binding , as well as in the intracellular signal transduction domain . ^^^ In view of the fact that defects in TRKA cause CIPA , the molecular pathology of CIPA provides unique opportunities to explore critical roles of the NGF TRKA receptor system . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Insulin receptor related receptor ( IRR ) expression is tightly coupled to the nerve growth factor ( NGF ) receptor , TrkA , throughout development . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We investigated whether the expression of NGF and its trkA and p 75 receptors in the lungs is age dependent , whether it is upregulated during RSV infection , and whether it affects neurogenic inflammation . ^^^ In pathogen free rats , expression of NGF and its receptors in the lungs declined with age , but RSV doubled expression of NGF , trkA , and p 75 in weanling and adult rats . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immunohistochemistry and in situ hybridization have been used to investigate expression of the candidate neurotrophin , nerve growth factor ( NGF ) , and its high and low affinity receptors trk A and p 75 , respectively , in painful IVD excised for the management of low back pain . ^^^ The adjacent nerves expressed the high affinity NGF receptor trk A . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) promotes neuronal survival and differentiation by activating TrkA receptors . ^^^ To study this process , we expressed TrkA receptors in Xenopus laevis oocytes and analyzed their response to NGF by using a combination of functional , biochemical , and structural approaches . ^^^ Application of NGF to TrkA receptor expressing oocytes promoted tyrosine phosphorylation and activated an oscillating transmembrane inward current , indicating that the TrkA receptors were functional . ^^^ Incubating TrkA cRNA injected oocytes with the transcriptional inhibitor actinomycin D did not prevent the appearance of these P face particles or electrophysiological responses to NGF , demonstrating that they did not arise from de novo transcription of an endogenous Xenopus oocyte gene . ^^^ The appearance of these particles in the plasma membrane correlated with responsiveness to NGF as detected by electrophysiological analysis and receptor phosphorylation , indicating that these novel P face particles were TrkA receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
However , a recent study by Howe and colleagues indicates that neurotrophin signaling via the trkA receptor requires formation of a signaling endosome containing NGF and trkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Inhibition of RhoA is mediated by activation of the TrkA receptor , because NGF failed to induce RhoA translocation and inhibition of ROK binding in nnr 5 cells that lack TrkA , whereas the inhibition was reconstituted in receptor add back B 5 cells . ^^^ The inhibitory pathway from TrkA to RhoA involves phosphatidylinositol 3 kinase ( PI3K ) , because the inhibitors LY 294002 or wortmannin prevented NGF induced RhoA translocation and increased RhoA association with ROK . ^^^ Taken together , these data indicate that NGF mediated activation of TrkA receptor stimulates PI3K , which in turn increases Rac 1 activity to induce transient RhoA inactivation during the initial phase of neurite outgrowth . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Detection of NGF receptors TrkA and p75NTR in human tumor cell lines and effect of NGF on the growth characteristic of the UT 7 / EPO cell line . ^^^ The receptors for nerve growth factor ( NGF ) TrkA and p75NTR were detected at the mRNA and the protein level in various human tumor cell lines . ^^^ The NGF receptor TrkA was found on all examined tumor cell lines and is not restricted to cells belonging to the nervous system . ^^^ NGF did not influence the proliferation rate of TrkA positive cells NMB , K 562 , UT 7 / EPO and PC 12 . ^^^ TrkA inhibition with K252a a blocker of Trk induced receptor kinase suggests , that the NGF signal may be transduced by the TrkA receptor in UT 7 / NGF cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Rat visual cortical neurones express TrkA NGF receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
RESULTS : We found that RA increased the expression of both trkA and p 75 NGF receptors in NCI N 592 and GLC 8 cell lines and prevented the loss of both NGF production and NGF receptor expression occurring when NGF treatment was discontinued . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
RT PCR analysis and immunological methods demonstrate that human umbilical vein endothelial cells ( HUVECs ) express the NGF receptors trkA ( NGFR ) and p75NTR . ^^^ NGF treatment caused a rapid phosphorylation of trkA ( NGFR ) in HUVECs , determining a parallel increase of phosphorylated ERK1 / 2 . ^^^ Accordingly , NGF induced a significant increase in HUVEC proliferation that was abolished by the trkA ( NGFR ) inhibitor K252a . ^^^ Endogenous NGF was responsible for the basal levels of trkA ( NGFR ) and ERK1 / 2 phosphorylation observed in untreated HUVEC cultures . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Sympathetic neurons depend on NGF binding to TrkA for their survival during vertebrate development . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Here , we have examined the effects of c erbB 2 on the adhesive properties of a mammary epithelial cell line , HB2 / tnz34 , in which c erbB 2 homodimerization can be induced by means of a transfected hybrid `` trk neu ' ' construct . trk neu consists of the extracellular domain of the trkA nerve growth factor ( NGF ) receptor fused to the transmembrane and cytoplasmic domains of c erbB 2 , allowing NGF induced c erbB 2 homodimer signaling . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Pharmacological and dominant negative inhibition and kinase assays indicate that Bgamma promotes neuritogenesis by stimulating the MAP kinase cascade downstream of the TrkA NGF receptor but upstream or at the level of the B Raf kinase . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Binding of NGF to its TrkA receptor is generally considered to have an antiapoptotic effect . ^^^ We now report that NGF treatment of PC 12 neural crest tumor cells trkA transfected to express TrkA at levels analogous to those seen in `` good prognosis ' ' neuroblastomas results in cell death ; similar treatment of native cells that express TrkA at levels similar to those of `` poor prognosis ' ' neuroblastomas has no effect on cell survival . ^^^ Morphological and biochemical studies indicate that NGF induces atypical apoptosis that is abrogated by the tyrosine kinase inhibitor K252alpha , but not by an inhibitor of NGF p 75 binding , in trkA transfected PC 12 cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The expression level of TrkA in PC 84 cells was comparable to that in PC 12 cells ; whereas that of another NGF receptor , p 75 , was significantly lower . ^^^ Our results suggest that NGF signaling via TrkA affects the differentiation characteristics of PC 12 cells but that an additional signaling via p 75 is necessary for the growth arrest of the cells . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Here we show that an increase in the intracellular cAMP concentration induces tyrosine phosphorylation of two receptor tyrosine kinases , i . e . the epidermal growth factor ( EGF ) receptor and the high affinity receptor for nerve growth factor ( NGF ) , also termed Trk ( A ) . cAMP induced tyrosine phosphorylation of the EGF receptor is rapid and correlates with ERK1 / 2 activation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We used a semiquantitative reverse transcription polymerase chain reaction technique to measure the messenger RNA for neurotrophins BDNF and NGF , and for their receptors trkB , trkA , and the low affinity receptor , p 75 ( NTR ) in the hippocampus and basal forebrain of rats after 28 weeks of alcohol consumption without malnutrition . ^^^ CET effects on basal forebrain trkA may reflect impaired NGF signaling that could compromise septohippocampal synaptic connections , cholinergic differentiation , and emergent functional abilities dependent on these properties . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Although motoneurons do not express trkA and should therefore be unresponsive to NGF , our results reveal that NGF can influence p 75 mediated motoneuron survival following axotomy . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In undifferentiated conditions , the levels of full length TrkA and of phosphorylated p44 / p42 mitogen activated protein kinase ( MAPK ) are increased in cells expressing Numb isoforms with a short PTB domain , indicating an up regulation of NGF signaling pathways . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Stable transfection of GM 1 synthase gene into GM 1 deficient NG 108 15 cells , CR 72 cells , rescues the responsiveness of Trk neurotrophin receptor to its ligand , NGF . ^^^ The data clearly showed that ( 1 ) confocal lazor microscopic studies disclosed NG CR 72 cells are really deficient in GM 1 , ( 2 ) stable transfection of GM 1 synthase cDNA into these cells ( NG CR72G cells ) restores the expression of GM 1 in the cells , and ( 3 ) Trk protein is expressed in NG CR 72 cells but its location seemed not to be on the plasma membrane , whereas we clearly observed that the Trk protein is expressed on the plasma membrane in NG CR72G cells . ( 4 ) NGF did not elicit the autophosphorylation of the Trk protein in GM 1 deficient NG CR 72 cells but did elicit the activation of the Trk protein in NG CR72G cells with an activation of mitogen activated protein kinase . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Does NGF binding to p 75 and trkA receptors activate independent signalling pathways to sensitize nociceptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The aim of this study was to verify the expression of two neurotrophins , nerve growth factor ( NGF ) and brain derived neurotrophic factor ( BDNF ) , as well as their receptors , trkA and p 75 , in an early stage of axonal regeneration in muscle vein combined grafts . ^^^ Longitudinal sections of grafts were immunostained by means of the following antibodies : anti NGF , anti BDNF , anti trkA , and anti p 75 . ^^^ Many of these cells reacted for NGF , BDNF , and p 75 , but not trkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
A chimera of the nerve growth factor ( NGF ) receptor , TrkA , and green fluorescent protein ( GFP ) was engineered by expressing GFP in phase with the carboxyl terminus of TrkA . ^^^ TrkA GFP becomes phosphorylated on tyrosine residues in response to NGF and is capable of initiating signaling cascades leading to prolonged MAPK activation and differentiation in PC 12 nnr5 cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Grit was abundant in neuronal cells and directly interacted with TrkA , a high affinity receptor for nerve growth factor ( NGF ) . ^^^ Overexpression of the TrkA binding region of Grit inhibited NGF induced neurite elongation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To gain insight into the effects of DR on expression of nerve growth factor ( NGF ) and the functional state of NT signalling pathways , we assessed the phosphorylation state of Trk receptors in light reared animals ( LR ) , in dark reared animals ( DR ) , in DR animals briefly exposed to light and in DR animals with exogenous supply of NTs [ NGF , brain derived neurotrophic factor ( BDNF ) and NT 4 ] in the VC . ^^^ We report that DR increases the expression of NGF but reduces the phosphorylation of TrkA and TrkB receptors with respect to LR ; normal phosphorylation is rapidly rescued by a brief exposure to light . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF infusion results in elevated levels of BDNF expression in both intact and injured trkA positive neurons , accompanied by reduced trkB expression . ^^^ These effects suggest NGF can regulate BDNF expression in trkA expressing neurons regardless of the axonal state and that elevated levels of BDNF may contribute to the down regulation in trkB expression associated with these states . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) and neurotrophin 3 ( NT 3 ) , members of the neurotrophin family , bind to and activate TrkA , TrkB and TrkC , respectively , members of the Trk receptor tyrosine kinase family , to exert various effects including promotion of differentiation and survival , and regulation of synaptic plasticity in neuronal cells . ^^^ BDNF stimulated much stronger interactions of PLCgamma with Trk than NGF and NT 3 in PC 12 cells stably expressing TrkB and cultured cerebral cortical neurons , respectively , although BDNF , NGF and NT 3 induced similar levels of tyrosine phosphorylation of Trk . ^^^ In Shc signaling , NGF , but not BDNF , displayed interactions between Trk and Shc in a phenylarsine oxide ( PAO ; an inhibitor of tyrosine phosphatase ) dependent manner in TrkB expressing PC 12 cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Adrenergic mouse pheochromocytoma ( MPC ) cells from heterozygous neurofibromatosis knockout mice show little or no expression of the NGF receptor trk A and do not undergo neuronal differentiation in response to NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Favorable neuroblastomas usually express TrkA , the receptor for nerve growth factor ( NGF ) , whereas unfavorable , MYCN amplified neuroblastomas usually express TrkB and its ligand , brain derived neurotrophic factor ( BDNF ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
On the one hand , p75NTR provides a positive modulatory influence on nerve growth factor ( NGF ) signaling through the high affinity neurotrophin receptor TrkA , and hence increases NGF survival signaling . ^^^ Here we demonstrate that TrkA is expressed in primary cultures of hippocampal neurons and is activated by NGF within 10 min of exposure . ^^^ In mouse hippocampal cells lacking p75NTR ( p75NTR / ) activation of TrkA by NGF was not detectable . ^^^ NGF increased TrkA phosphorylation in hippocampal neurons and provided protection that required phosphoinositol 3 phosphate ( PI 3 ) kinase activity and Akt phosphorylation , whereas the mitogen activated protein kinases ( MAPK ) , extracellular regulated kinases ( Erk ) 1 / 2 , were not involved . ^^^ P75NTR signaling independent of TrkA , such as increased neutral sphingomyelinase ( NSMase ) activity causing enhanced levels of ceramide , were not detected after exposure of hippocampal neurons to NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
By contrast , all the oocytes examined were negative for trkA and did not change the phosphorylation pattern after NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Increased expression of nerve growth factor ( NGF ) and high affinity NGF receptor ( p 140 TrkA ) in human osteoarthritic chondrocytes . ^^^ OBJECTIVE : We aimed to investigate the expression of nerve growth factor ( NGF ) and high affinity NGF receptor ( p 140 TrkA ) on chondrocytes from human healthy and osteoarthritic cartilage . ^^^ Chondrocytes were isolated by enzymatic digestion and freshly processed for NGF protein , Trk A detection and mRNA extraction . ^^^ NGF beta and TrkA expression was evaluated by immunofluorescence and flow cytometry analysis . ^^^ Of note , NGF beta and TrkA were upregulated in osteoarthritic chondrocytes suggesting a role of NGF in the pathophysiology of OA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the older GK rats , both mRNA and protein expression of nerve growth factor ( NGF ) in the sciatic nerve were significantly reduced ( p < 0 . 001 and p < 0 . 05 ) , and NGFR TrkA ( high affinity NGF receptor ) and NGFRp 75 ( low affinity NGF receptor ) protein expression was reduced in dorsal root ganglia ( DRG ) ( both p < 0 . 05 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To understand the functional interactions between the TrkA and p 75 nerve growth factor ( NGF ) receptors , we stably transfected LAN 5 neuroblastoma cells with an expression vector for ET R , a chimeric receptor with the extracellular domain of the epidermal growth factor receptor ( EGFR ) , and the TrkA transmembrane and intracellular domains . ^^^ A mutated NGF , 3T NGF , that binds to TrkA but not to p 75 did not synergize with EGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Two classes of astrocytes in the adult human and pig retina in terms of their expression of high affinity NGF receptor ( TrkA ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Consistent with the presence of trkB but not trkA , BDNF causes rapid phosphorylation of MAP kinases ERK 1 and ERK 2 , but NGF does not . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Binding of our trkA IgG fusion protein was specific for NGF with a K ( d ) = 4 . 26 10 10 ( 11 ) M and blocked NGF dependent neuritogenesis in PC 12 cells . ^^^ We hypothesized that binding of NGF in the injured cord by our trkA IgG fusion protein would diminish autonomic dysreflexia . ^^^ These results indicate that treatment with trkA IgG to block NGF suppresses the development of autonomic dysreflexia after a clinically relevant spinal cord injury . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Human periodontal ligament cells , human gingival fibroblasts , and human gingival keratinocytes expressed mRNA for NGF and TrkA . ^^^ The expression of NGF and TrkA . mRNA was regulated by interleukin ( IL ) 1beta . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In this study , we investigated whether hematopoietic stem cells ( HSC ) and progenitors present in human cord blood can express nerve growth factor ( NGF ) specific receptors , TrkA and p 75 . ^^^ Our results showed a marked expression of TrkA and NGF in cord blood CD 34 ( + ) cells . ^^^ A gradient of TrkA and NGF expression exists and is highest in cord blood CD 34 ( + ) cells , reduced in cord blood mononuclear cells ( MNC ) and minimal in mononuclear cells isolated from adult peripheral blood . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Methylmercury decreases NGF induced TrkA autophosphorylation and neurite outgrowth in PC 12 cells . ^^^ The present study examined the effects of CH ( 3 ) Hg on ( 125 ) 1 nerve growth factor ( NGF ) binding to the TrkA receptor , NGF induced activation of the TrkA receptor , and neurite outgrowth in an in vitro model of differentiation using PC 12 cells . ^^^ Methylmercury ( CH ( 3 ) Hg ) at 30 nM ( EC ( 50 ) for neurite outgrowth inhibition ) did not affect NGF binding to TrkA . ^^^ Concurrent exposure to CH ( 3 ) Hg and NGF for 2 . 5 min resulted in a concentration dependent decrease in TrkA autophosphorylation , which was significant at 100 nM CH ( 3 ) Hg . ^^^ To determine whether the observed inhibition of TrkA was sufficient to alter cell differentiation , NGF stimulated neurite outgrowth was examined in PC 12 cells after exposure to 30 nM CH ( 3 ) Hg , a concentration that inhibited TrkA autophosphorylation by approximately 50 % . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Surprisingly , NGF initiated intracellular targeting of DOR in PC 12 cells acutely , within 60 min after initial activation of TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Molecular dynamics simulations of the NGF TrkA domain 5 complex and comparison with biological data . ^^^ Here we study energetics and dynamics of the NGF TrkA complex by carrying out multinanosecond molecular dynamics simulations , accompanied by electrostatic calculations based on the Poisson Boltzmann equation . ^^^ Finally , these calculations , used along with the mutagenesis data , provide a basis for designing new peptides that mimic NGF in TrkA binding function . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF modifies cholinergic neurons through its low p 75 and high affinity TrkA receptors . ^^^ In TrkA ( ) cells , NGF ( 100 ng / ml ) affected neither choline acetyltransferase nor morphology but depressed pyruvate dehydrogenase activity by about 30 % . ^^^ On the contrary , in nondiferentiated TrkA ( + ) NGF brought about a 2 . 5 fold increase of choline acetyltransferase . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Trk receptors are a family of three receptor tyrosine kinases , each of which can be activated by one or more of four neurotrophins nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , and neurotrophins 3 and 4 ( NT 3 and NT 4 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
RESULTS : These results revealed a low amount of NGF in the plasma of old subjects associated with a reduced expression of mRNA for NGF receptor trkA in peripheral lymphocytes . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To address this issue , various combinations of transfected PC 12 cells expressing a platelet derived growth factor receptor TrkA chimera and the p75NTR selective nerve growth factor mutant ( Delta9 / 13 NGF ) were utilized to selectively stimulate TrkA or p75NTR signaling , respectively . ^^^ In addition , a new interaction in the TrkA / p75NTR heteromeric receptor signal transduction network was revealed , namely that NGF induced activation of the MAPK pathway appears to inhibit the parallel NGF induced Akt pathway . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The nerve growth factor ( NGF ) family of neurotrophins binds two classes of cell surface receptors , trk receptor tyrosine kinases and the shared p 75 receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
A possible role for NGF was suggested by the findings that parotid cells express both TrkA and p 75 receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
SHB mediates certain responses in platelet derived growth factor ( PDGF ) receptor , fibroblast growth factor ( FGF ) receptor , neural growth factor ( NGF ) receptor TRKA , T cell receptor , interleukin 2 ( IL 2 ) receptor and focal adhesion kinase ( FAK ) signaling . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Thus , a chimeric receptor was created that possessed the extracellular and transmembrane domains of the nerve growth factor ( NGF ) receptor TrkA and the cytoplasmic domain of PDGFRbeta ( TTbeta ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Here we show that survival of sympathetic neurons supported by NGF on distal axons requires the kinase activity of the NGF receptor , TrkA , in both distal axons and cell bodies . ^^^ In contrast , disruption of TrkA activity exclusively in proximal axonal segments affects neither retrograde NGF TrkA signaling in cell bodies nor neuronal survival . ^^^ Taken together , our results indicate that retrogradely transported NGF TrkA complexes promote sympathetic neuron survival . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have examined the effect of global transient cerebral ischemia , evoked in rat by 10 min of cardiac arrest , upon the changes in the cellular expression of two nerve growth factor ( NGF ) receptors ( TrkA and p 75 ) in the hippocampus . ^^^ On the other hand , the up regulated astroglial TrkA receptor may be an important target for exogenous NGF , which , as previously described [ J Neurosci 11 ( 1991 ) 2914 ; Neurosci Lett 141 ( 1992 ) 161 ] , exerts a neuroprotective effect in ischemia . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Both of NGF family and their receptors Trk family mRNA were expressed in gastric cancer and normal gastric mucosa . ^^^ Degrees of down regulation in NGF family were greater than those in their receptors Trk family . ^^^ CONCLUSION : Down regulated expression of NGF family and their receptors Trk family mRNA in gastric cancer is confirmed . ^^^ NGF family and their receptors Trk family probably play a unique role in gastric cancer cell apoptosis by a novel Ras or Raf signal transduction pathway . ^^^ NGF , BDGF , NT 3 , NT 4 / 5 , NT 6 and TrkA , B and C were down regulated simultaneously in gastric carcinoma in comparison with normal gastric mucosa . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
PURPOSE : The purpose is to analyze the possible correlation between expression and activation of the high affinity nerve growth factor ( NGF ) receptor TrkA , cell cycle protein expression , and disease outcome in serous ovarian carcinoma . ^^^ In addition , we wished to study the possible link between expression of NGF , a novel angiogenic factor and its receptor TrkA , and the expression of factors involved in angiogenesis in effusions and solid tumors . ^^^ EXPERIMENTAL DESIGN : Sections from 80 malignant effusions and 65 corresponding solid tumors were evaluated for protein expression of NGF , TrkA , and phospho TrkA ( p TrkA ) . ^^^ RESULTS : NGF , TrkA , and p TrkA were expressed in carcinoma cells in effusions in 60 of 80 ( 75 % ) , 64 of 80 ( 80 % ) , and 15 of 80 ( 19 % ) specimens , respectively . ^^^ None of these correlated with NGF or TrkA expression or activity . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Pathways responsible for transducing the sensitisation of TRPV 1 by TrkA , the NGF receptor , were characterised by observing the effects of inhibitors of key members of NGF activated second messenger signalling cascades . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The biological effects of Nerve Growth Factor ( NGF ) are primarily mediated via its high affinity receptor TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
OBJECTIVE : To assess the effects of both TrkA and p 75 ( NTR ) on nerve growth factor ( NGF ) induced differentiation of neuroblastoma cells . ^^^ METHODS : Retroviral vectors were constructed to express the high affinity NGF receptor ( TrkA ) and low affinity NGF receptor ( p 75 ( NTR ) ) . ^^^ The p 75 ( NTR ) transfection only resulted in the mild differentiation response , and transfection of TrkA gene caused remarkable neurite extension , up regulation of neurofilament and decreased expression of N myc oncogene after NGF treatment . ^^^ The cotransfection of the two genes into this cell line resulted in the more rapid and more apparent morphological changes than single TrkA transfected cells after NGF treatment . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
However , NGF rescue from growth factor withdrawal requires NGF signalling through the high affinity tyrosine kinase receptor ( TrkA ) , while NGF rescue from TNFalpha promoted cell death requires NGF signalling through the low affinity p75NTR receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
PURPOSE : To determine which of the neurotrophins ( NTs ) nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , neurotrophin 3 ( NT 3 ) , and neurotrophin 4 / 5 ( NT 4 ) and their receptors ( NTrs ) , TrkA , TrkB , TrkC , and p 75 , are present in the adult rat lacrimal gland . ^^^ RESULTS : RT PCR showed positive bands at the appropriate sizes for NGF , BDNF , NT 3 , and NT 4 , and for the receptors TrkA , TrkB , TrkC , and p 75 . ^^^ Western blot analysis confirmed these results , showing that the lacrimal gland expresses NGF , BDNF , NT 3 , and NT 4 as well as the NTrs TrkA , TrkB , and TrkC and the p 75 protein . ^^^ NGF , BDNF , NT 3 , and NT 4 were localized in the lacrimal gland acini with differing cellular distributions , whereas TrkA , TrkB , and TrkC , were localized in myoepithelial cell and ductal cell membranes . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Quantitative in situ hybridization was used to detect changes in neuronal PACAP mRNA expression and to correlate this expression with neuronal mRNA expression of the NGF receptor tyrosine kinase ( trk ) A . ^^^ The results from this study show that inflammation triggered increases in PACAP expression occurs in small to medium sized dorsal root ganglion ( DRG ) neurons that also express trkA , and that this elevation in PACAP expression is prevented by systemic injection of anti NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In particular , the putative role of NGF and its receptor TrkA in immune system homeostasis has become a much studied topic , whereas information on the other neurotrophins is scarce in this regard . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The NGF induced release occurred even in the presence of the Trk inhibitor K252a . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Importantly , the constitutive growth of breast cancer cells was strongly inhibited by either NGF neutralizing antibodies or K 252a , a pharmacological inhibitor of NGF receptor TrkA , indicating the existence of an NGF autocrine loop . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The neurotrophins neurotrophin 3 ( NT 3 ) , brain derived growth factor ( BDNF ) and nerve growth factor ( NGF ) bind to the p 75 receptor , but each neurotrophin also binds a more selective Trk receptor ( e . g . ^^^ TrkA NGF and TrkC NT 3 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This ability seems to depend partially on neurotrophic factors , which include some neurotrophins , mainly nerve growth factor ( NGF ) , and their cognate Trk receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Recent evidence indicates that some thymic cells of developing and adult laboratory animals express the neurotrophin NGF and its low affinity p75NTR and high affinity TrkA receptor . ^^^ The immunoreactivity of NGF , p75NTR , TrkA and cytokeratin was found in the epithelial thymocyte microenvironment . ^^^ They suggest a possible immunotrophic / immunoregulatory role of the NGF p75NTR TrkA system for T cell development in human thymus during senile involution . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
PDGF induced upregulation of N and P / Q type Ca2+ channel currents completely mimicked upregulation of these currents caused by NGF stimulation of the endogenous TrkA receptor tyrosine kinase ( RTK ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The phospho TrkA levels in the differentiated PC 12 cells were diminished by both complete NGF withdrawal and pharmacological inhibition of Trk kinase activity . ^^^ Interestingly , the initial response of the cyclic AMP response element promoter to NGF was delayed , becoming Trk dependent well beyond the peaks in TrkA and downstream protein kinase signal transduction . . ^^^ Previous studies have shown that the activation kinetics of the NGF receptor , TrkA , and downstream protein kinases appear rapid and seemingly transient after NGF treatment of naive PC 12 cells . ^^^ Intracellular sequestration of the majority of TrkA molecules ( both phosphorylated and non phosphorylated TrkA ) and persistent dephosphorylation of the small pool of cell surface TrkA renders the persistent phospho TrkA signal in the differentiated PC 12 cells resistant to partial NGF withdrawal as well as exposure to additional NGF . ^^^ NGF regulated both extracellular regulated kinases 1 / 2 and Akt activity in the differentiated PC 12 cells via sustained TrkA activity . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Here , we show that Semaphorin 3F ( Sema 3F ) can antagonize nerve growth factor ( NGF ) stimulated TrkA ( tyrosine receptor kinase A ) signaling in sympathetic neurons , thereby apparently contributing to growth cone collapse . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
METHODS : Rat lenses were dissected and the expression of NGF , NGF mRNA and high affinity NGF receptor ( TrkA ) was evaluated by immunohistochemistry , immunoenzymatic assay ( ELISA ) and in situ hybridization ( ISH ) techniques . ^^^ Although the functional significance of TrkA on lens epithelium is at present not clear , the expression of NGF and its high affinity receptor on the same cells together with our experimental results suggest that NGF is involved in supporting trophism and / or the function of the lens epithelium . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Plasticity in developing rat uterine sensory nerves : the role of NGF and TrkA . ^^^ Finally , levels of TrkA NGF receptor in sensory neurons of T 13 and L 1 dorsal root ganglia ( DRG ) , which supply the uterus , were assessed using densitometric immunohistochemistry . ^^^ These studies showed that : ( 1 ) chronic oestrogen treatment led to an 83 % reduction in the intercept density of CGRP immunoreactive nerves ; ( 2 ) sympathectomy had no effect on the density of uterine sensory nerves or on the pattern of oestrogen induced changes ; ( 3 ) NGF mRNA and protein increased following sympathectomy or chronic oestrogen treatment ; and ( 4 ) oestrogen produced increased intensity of labelling ( 28 % ) for TrkA receptors in small diameter sensory neurons , but decreased labelling ( 13 % ) in medium sized neurons , which represent the large majority of the DRG neurons supplying the upper part of the uterine horn . ^^^ The possibility that alterations in neuronal levels of TrkA contribute to the lack of response of uterine sensory nerves to the oestrogen induced increase in NGF levels is discussed . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Previously , we have shown using the double immunostaining method that the NGF receptors ( NGFR ) p 75 and TrkA are expressed mainly on subpopulations of GFAP+ astrocytes , and this expression increases progressively after ischemia . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
With regard to the trkA receptor , satellite cells might be supported trophically by NGF released from the neuron with which they are associated ; alternatively , satellite cells might internalize NGF to constitute a reservoir for later release to the neuron . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The distribution of nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , neurotrophin 3 ( NT 3 ) and 4 ( NT 4 ) , and their high affinity receptors TrkA , TrkB , TrkC and low affinity receptor p 75 , was analyzed in adult porcine retinal sections by immunohistochemistry . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In addition , we found that TrkA , the high affinity NGF receptor , was only found on fibers projecting into the barrel cortex . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Neurotrophin 3 down regulates trkA mRNA , NGF high affinity binding sites , and associated phenotype in adult DRG neurons . ^^^ Serial sections were processed for receptor radioautography or in situ hybridization to identify and colocalize neurons expressing high affinity nerve growth factor ( NGF ) binding sites , substance P ( SP ) , trkC , or trkA mRNAs and to examine the influence of NT 3 on these populations . ^^^ NT 3 does not appear to alter trkC expression , but evokes a notable reduction in trkA , high affinity NGF binding sites , and SP levels . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Postganglionic sympathetic neurons , which are exquisitely sensitive to small changes in levels of target derived nerve growth factor ( NGF ) , express two transmembrane receptors : 1 ) the trkA receptor mediates neuron survival and neurite outgrowth ; and 2 ) the p 75 neurotrophin receptor ( p75NTR ) enhances neuronal responsiveness of trkA to NGF . ^^^ Elevating levels of NGF induces several morphological and neurochemical alterations in sympathetic neurons , including axonal sprouting , increased levels of p75NTR mRNA relative to trkA mRNA , and increased accumulations of NGF in hypertrophied somata . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The lack of effect of NGF as compared to other neurotrophins is not unexpected since we have not found TrkA expression under our experimental conditions . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF is known to activate numerous signaling pathways through trkA and p 75 receptors . ^^^ NGF controls ASIC 3 basal expression through constitutive activation of a trkA / phospholipase C / protein kinase C pathway , ( 2 ) . high inflammatory like NGF induces ASIC 3 overexpression through a trkA / JNK / p38MAPK pathway and a p 75 dependent mechanism as a transcriptional switch , and ( 3 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Inactivation of trkA , but not of p75NTR , and wortmannin prevented NGF induced p 53 nuclear translocation . ^^^ This effect of NGF is exclusively mediated by trkA through activation of phosphatidylinositol 3 kinase and may be related to its growth inhibitory action . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In fact , NGF transduces its effects by binding two classes of cell surface receptors , TrkA and p 75 ( NTR ) , both of which are produced by CBF neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The present study was aimed at comparing , by dose response experiments , the neurotropic activity of cobra and vipera versus mammalian NGFs , by using a novel bioassay involving PC 12 cells genetically engineered to overexpress NGF trkA receptors of human origin . ^^^ These cells respond to NGF by differentiation ( morphologically expressed as neurite outgrowth ) by a process mediated by NGF trkA receptors . ^^^ These data indicate the following order of NGF activity towards recombinant human trkA receptors : recombinant human NGF > mouse NGF > cobra NGF > vipera NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
They do not , however , express trkA , the gene encoding the tyrosine kinase receptor TrkA , the high affinity receptor for nerve growth factor ( NGF ) , the prototypic NT . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
They were incubated with 5 % alamarBlue and different concentrations of progesterone , EGF or NGF in the presence or absence of neutralizing EGF or NGF antibody , K252a ( an inhibitor of trkA , the high affinity receptor for NGF ) , Ru 486 ( an antagonist of progesterone and glucocorticoid receptor ) or ZK 137 316 ( a specific antagonist of progesterone receptor ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Therefore , the effects of nicotine on expression of nerve growth factor ( NGF ) and its receptor , tyrosine receptor kinase A ( trkA ) , were studied in cultured spinal cord neurons treated with arachidonic acid . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
A major in vitro PC model consists of PC 12 cells that respond to nerve growth factor ( NGF ) by differentiation , mediated by the trkA receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) interacts with its receptor tyrosine kinase , TrkA , at axon terminals to produce local signals within axon terminals and retrograde signals to the neuronal cell body . ^^^ According to prevalent theory , retrograde signaling requires the retrograde transport to the cell bodies of signaling endosomes containing activated TrkA complexed with NGF . ^^^ Alternative mechanisms in which retrograde signals reach the cell bodies unaccompanied by NGF may or may not require activated TrkA in the cell body . ^^^ To help distinguish this possibility , we investigated the spatial requirements of TrkA kinase activity for neuronal survival and axon growth in rat sympathetic neurons supported by NGF provided only to distal axons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To clarify the possible role of nerve growth factor ( NGF ) and its receptor on changes in peripheral innervation of the TMJ , the expressions of trkA and p 75 receptor in trigeminal ganglia were examined . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Furthermore , by expressing the nerve growth factor ( NGF ) receptor , TrkA , and the epidermal growth factor ( EGF ) receptor , ErbB 1 , in RCS cells we show that NGF treatment of the transfected cells caused growth inhibition , whereas EGF did not . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Using PC 12 cells as a model of the presynaptic element , we show that depolarization increases TrkA tyrosine phosphorylation in response to nerve growth factor ( NGF ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Ectopic expression of the TrkA receptor in adult dopaminergic mesencephalic neurons promotes retrograde axonal NGF transport and NGF dependent neuroprotection . ^^^ These cells also accumulate TrkA transcripts upon transfection and extended neurites in the presence of NGF . ^^^ The presence of TrkA receptors in corresponding striatal dopaminergic endings was demonstrated by the advent of a striato nigral retrograde axonal transport of ( 125 ) 1 NGF . ^^^ Likewise , ectopic expression of TrkA in neurons of the parafascicular thalamic nucleus promoted a striatofuge transport of NGF toward this structure . ^^^ These data suggest that ectopic TrkA can mediate the trophic actions of NGF and influence neuronal plasticity in vivo . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The mRNA and protein levels of the neurotrophins of the NGF family ( NGF , BDNF , NT 3 and NT 4 / 5 ) and their receptors ( trkA , trkB , trkC and p 75 ) were quantified in septum and hippocampus using RT PCR . ^^^ Particularly , the gene expression of NGF , NT 3 , and the high affinity receptors trkA , trkB and trkC increased significantly . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
A 2 week intracerebroventricular infusion of NGF without deafferentation resulted in enhanced mRNA levels of trkA , trkC , and p 75 as well as significantly increased NGF and NT 3 protein in the SCG . ^^^ When NGF infusion followed deafferentation , both trkA and p 75 showed significant increases while trkC levels were similar to control values . ^^^ In addition , the present findings provide evidence that , when preganglionic input is removed prior to the NGF infusion , NT 3 effectively competes with NGF for trkA binding . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Sixth , LPA and / or NGF stimulated the translocation of tyrosine phosphorylated Trk A receptor and LPA ( 1 ) receptor to the nucleus . ^^^ Taken together , these findings suggest that NGF and LPA exert cross talk regulation both at the level of p42 / p44 MAPK signaling and in the nuclear translocation of LPA ( 1 ) and Trk A receptors . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF protein levels in the culture medium , NGFmRNA and high affinity NGF receptor ( Tyrosine kinase A : TrkA ) expression in the cells were evaluated in basal conditions and after stimulation with pro inflammatory cytokines or with the neuropeptide cholecystokinin 8 ( CCK 8 ) . ^^^ The effect of NGF supplement to culture medium on cell proliferation , TrkA expression , and tumour necrosis factor alpha ( TNF alpha ) and inducible nitric oxide synthase ( iNOS ) production was investigated . ^^^ TrkA NGF receptors are also expressed in both normal and OA synovial cells . ^^^ NGF , but not IL 1 beta , TNF alpha and CCK 8 , enhances the expression of TrkA in isolated synovial cells . ^^^ CONCLUSIONS : NGF is produced and released and TrkA receptors are expressed in synovial inflammation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF treatment produced phosphorylation of TrkA in choroidal and retinal endothelial cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In addition , in NGF treated PC 12 cells , gal 3 expression , ERK1 / 2 activation and neurite outgrowth could be specifically inhibited at the level of TrkA , Ras and MAPK kinase , whereas expression of an oncogenic form of Ras leads to gal 3 expression and neurite outgrowth in the absence of growth factors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In B5P cells , a clonal cell line of PC 12 cells overexpressing tyrosine kinase NGF receptor ( TrkA ) , cPA elicited transphosphorylation of TrkA . cPA elicited ERK activation was blocked by K252a and PKI . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
PC 12 cells undergo neuritogenesis upon nerve growth factor ( NGF ) activation of the TrkA receptor , an effect mimicked by the ganglioside GM 1 binding B subunit of cholera toxin ( CTB ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We also report examples of cross talk signal integration between the Trk A ( tropomyosin receptor kinase A ) receptor and the LPA ( 1 ) receptor in terms of the NGF ( nerve growth factor ) dependent regulation of the p42 / p44 MAPK pathway . ^^^ NGF induces recruitment of the LPA ( 1 ) receptor to the nucleus ( delivery might be Trk A dependent ) , whereupon the LPA ( 1 ) receptor may govern gene expression via novel nuclear signalling processes . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA is the receptor tyrosine kinase ( RTK ) for nerve growth factor ( NGF ) and stimulates NGF dependent cell survival and differentiation in primary neurons and also differentiation of neuroblastomas and apoptosis of medulloblastomas . ^^^ We have previously shown that aspartic acid and glutamic acid substitution ( AspGlu and GluAsp ) of the activation loop tyrosines in TrkA ( Tyr ( 683 ) and Tyr ( 684 ) ) supports NGF independent neuritogenesis and cell survival in PC 12 cell derived nnr 5 cells . ^^^ The NGF dependent neuritogenic responses are lower for the mutant Trks ( approximately 30 60 % for AspGlu and 50 60 % for GluAsp ) , relative to wild type TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) mediates the survival and differentiation of neurons by stimulating the tyrosine kinase activity of the TrkA / NGF receptor . ^^^ Conversely , inhibition of endogenous SHP 1 with a dominant inhibitory mutant stimulated basal tyrosine phosphorylation of TrkA , thereby promoting NGF independent survival and causing sustained and elevated TrkA activation in the presence of NGF . ^^^ These data indicate that SHP 1 can function as a TrkA phosphatase , controlling both the basal and NGF regulated level of TrkA activity in neurons , and suggest that SHP 1 regulates neuron number during the developmental cell death period by directly regulating TrkA activity . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF activates the phosphorylation of MAP1B by GSK3beta through the TrkA receptor and not the p 75 ( NTR ) receptor . ^^^ PC 12 cells express two types of membrane receptor for NGF : TrkA receptors and p75NTR receptors , and it was not clear from our studies which receptor was responsible . ^^^ Similarly , NGF fails to activate GSK3beta phosphorylation of MAP1B in PC 12 cells that lack TrkA receptors but express p75NTR receptors ( PC 12 nnr ) . ^^^ Chick ciliary ganglion neurons in culture lack TrkA receptors but express p75NTR and also fail to show NGF dependent GSK3beta phosphorylation of MAP1B , whereas in rat superior cervical ganglion neurons in culture , NGF activation of TrkA receptors elicits GSK3beta phosphorylation of MAP1B . ^^^ These results suggest that the activation of GSK3beta by NGF is mediated through the TrkA tyrosine kinase receptor and not through p75NTR receptors . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Loss of cell adhesion impairs the early response of TrkA to nerve growth factor ( NGF ) . ^^^ The present analysis of early NGF signaling shows that the upstream activation of TrkA , as well as the recruitment of the adaptor protein Shc , are dramatically attenuated upon loss of cell adhesion , while the downstream activation of ERK1 / 2 is unaffected . ^^^ That loss of cell adhesion interferes with the primary signaling response to NGF ( i . e . autophosphorylation of TrkA ) may explain why suspended PC 12 cells fail to morphologically differentiate in response to NGF . ^^^ The possibility that established adhesion driven mechanisms underlie the full responsiveness of TrkA to NGF is discussed . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In contrast , both NGF and phosphorylation of trkA increased significantly in DRGs , with a marginal appearance of phosphorylated trkA in axons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF binds trkA receptors located on sensory nerve terminals . ^^^ Because NGF binds to trkA tyrosine kinase receptors , the NGF released during TDI exposure may mediate SP upregulation in airway sensory neurons , innervating the nasal cavity . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The NGF induced decrease in N myc expression was blocked by the Trk tyrosine kinase ( TK ) antagonist K252a indicating that signals transduced by Trk TK downstream targets were involved . ^^^ NGF activation of TrkA decreases N myc expression via MAPK path leading to a decrease in neuroblastoma cell number . ^^^ In this report , we detail mechanisms by which nerve growth factor ( NGF ) decreases N myc levels in TrkA transfected NB cells and its effect on NB cell proliferation . ^^^ Furthermore , NGF affects the time required for 15N TrkA cells to complete a replication cycle by decreasing N myc , E2Fs , cyclin E kinase activity and increasing p 27 ( kip 1 ) binding to cyclin E kinase . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) triggered Trk A signaling is involved in growth , survival and differentiation of neurons in the central nervous system and in neural crest derived cells . ^^^ This distribution pattern of Trk A suggests that its ligand , NGF , exerts significant trophic effects in the rodent inner ear . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) activates TrkA to trigger signaling events that promote the survival , differentiation and maintenance of neurons . ^^^ The ' signaling endosome ' hypothesis stipulates that NGF , TrkA and signaling proteins are retrogradely transported on endocytic vesicles . ^^^ Following NGF treatment , clathrin coated vesicles ( CCVs ) contain NGF bound to TrkA together with activated signaling proteins of the Ras / pErk1 / 2 pathway . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Cells from the immune system have been detected in CNS injury and found to produce and secrete a variety of neurotrophins such as NGF , BDNF , NT 3 and NT 4 / 5 , and to express ( similarly to neuronal cells ) , members of the tyrosine kinase ( Trk ) receptor family such as TrkA , TrkB and TrkC . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Expression of NGF , Trka and p 75 in human cartilage . ^^^ Nerve growth factor ( NGF ) exerts its action through two types of receptor : high affinity tyrosine kinase A receptor ( trkA ) and low affinity p 75 receptor . ^^^ The aim of the present immunohistochemical study was to investigate the expression and distribution of NGF , trkA , and p 75 in normal cartilaginous tissues from adult subjects : articular and meniscal cartilage of the knee , cartilage from the epiglottis , and intervertebral disc tissue . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In this study , we analysed the expression of NGF , TrkA and insulin in human pancreatic islets from normal , ductal adenocarcinoma and insulinoma afflicted samples , using double immunofluorescent labelling and confocal microscopy . ^^^ Moreover , similar to previous observations in rat , the high affinity NGF receptor TrkA is also expressed in beta cells . ^^^ We demonstrate that human beta cells express TrkA and NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The RET receptor signal pathway is functional in most NB , while loss of nerve growth factor ( NGF ) receptor ( trkA ) gene expression correlates with an aggressive phenotype . ^^^ Furthermore , GDNF synergizes with ciliary neurotrophic factor ( CNTF ) to enhance TRKA receptor expression , thereby strengthening the NGF mediated differentiation signal . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In immunohistochemical studies , we found that keratinocytes in lesional and nonlesional psoriatic tissue express high levels of nerve growth factor ( NGF ) and that there is a marked upregulation of NGF receptors , p 75 neurotrophin receptor ( p75NTR ) and tyrosine kinase A ( TrkA ) , in the terminal cutaneous nerves of psoriatic lesions . ^^^ These observations , as well as recent findings about NGF induced chemokine expression in keratinocytes , further substantiate a role of the NGF p75NTR TrkA system in the inflammatory process of psoriasis . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Mutations of the NGF high affinity receptor tyrosine kinase A ( Trk A ) have been found in congenital insensitivity to pain and anhidrosis ; these are likely to be partial loss of function mutations , as axon reflex vasodilatation and sweating can be elicited albeit reduced , suggesting rhNGF could restore nociception in some patients . ^^^ Decreased NGF in leprosy skin may explain cutaneous hypoalgesia even with inflammation and rhNGF may restore sensation , as spared nerve fibers show Trk A staining . ^^^ NGF and glial cell line derived neurotrophic factor ( GDNF ) are both produced by basal keratinocytes and neurotrophin ( NT 3 ) by suprabasal keratinocytes : relative mRNA expression was significantly lower in early diabetic neuropathy skin compared to controls , for NGF ( P < 0 . 02 ) , BDNF ( P < 0 . 05 ) , NT 3 ( P < 0 . 05 ) , GDNF ( < 0 . 02 ) , but not NT4 / 5 , Trk A or p 75 neurotrophin receptor ( all P > 0 . 05 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
AEC expressed both high affinity ( TrkA ) and low affinity ( p 75 ( NGFR ) ) receptors for NGF . ^^^ Exogenously added NGF induced rapid phosphorylation of TrkA tyrosine kinase . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) , an important trophic factor for sympathetic neurons , has been implicated in the responsiveness of immune competent cells through its functional receptor , tropomyosin receptor kinase ( TrkA ) . ^^^ METHOD OF STUDY : Using immune fluorescence , we evaluated decidual and placental expression of NGF and TrkA on gestation day ( gd ) 13 . 5 in the abortion prone mouse model CBA / J 10 DBA / 2J in ( 1 ) CBA / J female control mice ; ( 2 ) CBA / J mice exposed to stress on gd 5 . 5 ; and ( 3 ) CBA / J mice injected with SP on gd 5 . 5 to mimick stress perception . ^^^ RESULTS : Stress and SP injection significantly increased the abortion rate and up regulated decidual NGF and TrkA expression compared with the control . ^^^ Stress , but not SP injection down regulated placental NGF , whereas no changes in placental TrkA were observed . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We show here that their respective receptors , TrkA , TrkB , TrkC , as well as p 75 ( NTR ) ( the low affinity NGF receptor ) , are expressed in vitro by the nasal ensheathing cells ; the three neurotrophins promote purification and proliferation of these glial cells , with an optimal concentration of 50 ng / ml ; and human ensheathing cells can be easily biopsied and highly purified using a serum free medium supplemented with NT 3 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
After 7 days of ocular hypertension there is a transient up regulation of retinal NGF , while its receptor TrkA is up regulated in a sustained fashion in retinal neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
High dose NGF may induce cytoplasmic relocation of the receptor TrkA and axonal growth arrest independently of p75NTR . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In PC 12 cells , it activated the high affinity NGF receptor , TrkA , and displayed NGF like bioactivity by promoting neurite outgrowth and cell survival after serum deprivation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF regulates cell survival and cell death via binding to two different receptors , TrkA and p75NTR ( ref . 10 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Constitutively active Src facilitates NGF induced phosphorylation of TrkA and causes enhancement of the MAPK signaling in SK N MC cells . ^^^ Activation of TrkA and extracellular signal regulated kinase ( ERK ) by nerve growth factor ( NGF ) was inhibited by pretreatment with PP 2 , an inhibitor of Src family kinases . ^^^ Moreover , NGF induced phosphorylation of TrkA and ERK was also attenuated by the transfection with a dominant negative src construct . ^^^ In addition , we showed that active Src phosphorylates TrkA directly in vitro , and that Src associates with TrkA through Grb 2 after NGF stimulation . ^^^ These results suggest that constitutively active Src that associates with TrkA through Grb 2 after NGF stimulation participates in TrkA phosphorylation and in turn enhances the mitogen activated protein kinase signaling in SK N MC cells . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
While exploring possible mechanisms of PTEN effects on NGF signaling , we discovered a significant down regulation of both high affinity ( TrkA ) and low affinity ( p 75 ) NGF receptors in PTEN overexpressing clones . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF increased proliferation of Neuro 2a cells , which express p75NTR but no TrkA receptors on their surface . ^^^ On the other hand , SK N BE cell proliferation was decreased after NGF treatment , even though these cells also express p75NTR but no TrkA receptors on their surface . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
They act through three tyrosin kinase ( Trk ) specific receptors : NGF bind to TrkA , BDNF to TrkB and NT 3 to TrkC . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) functions as a ligand for two receptors , the TrkA tyrosine kinase receptor and the p 75 neurotrophin receptor ( p75NTR ) . ^^^ NRH 2 does not bind to NGF ; however , coimmunoprecipitation experiments demonstrate that NRH 2 is capable of interacting with TrkA receptors . ^^^ Coexpression of NRH 2 with TrkA receptors resulted in the formation of high affinity binding sites for NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The pharmacological inhibition of phosphatidylinositol 3 kinase ( PI3K ) by wortmannin significantly suppressed the survival supporting activity of MC 14 , whereas the NGF receptor ( tyrosine kinase A or TrkA ) inhibitor K252a showed no detectable effect on MC 14 activity . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These results show that exposure to NGF leads to phenotypic changes in TrkA expressing trigeminal neurons at early embryonic development , but selective survival of small diameter neurons at later ages . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Optimal sensitivity of the survival response to NGF requires the presence of TrkA and the p 75 neurotrophin receptor , p 75 ( NTR ) . ^^^ Signalling pathways used by TrkA are well established , but the mechanisms by which p 75 ( NTR ) enhances NGF signalling remain far from clear . ^^^ Whilst providing evidence that p 75 ( NTR ) augments TrkA signal transduction , these results do not preclude the presence of a p 75 ( NTR ) TrkA high affinity NGF receptor . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The adapter protein SH 2 B has been shown to bind to activated nerve growth factor ( NGF ) receptor TrkA and has been implicated in NGF induced neuronal differentiation and the survival of sympathetic neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The aim of this study was to characterize phenotypic alterations along the progression of breast carcinoma from primary tumor to pleural effusion through analysis of the expression of nerve growth factor ( NGF ) and its receptors phospho TrkA ( p TrkA activated receptor ) and p 75 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Methylmercury inhibits TrkA signaling through the ERK1 / 2 cascade after NGF stimulation of PC 12 cells . ^^^ Using PC 12 cells as a model of neuronal differentiation , we have shown that acute exposure to methylmercury ( CH3Hg ) inhibits nerve growth factor ( NGF ) induced activation of TrkA . ^^^ These results show that CH3Hg inhibition of NGF stimulated TrkA activation in PC 12 cells decreases downstream signaling through the Raf / MEK / ERK cascade . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Congenital insensitivity to pain with anhidrosis ( CIPA ) is identified as a genetic disorder of mutations in the human TrkA known as high affinity receptor of nerve growth factor ( NGF ) . ^^^ NGF signal through TrkA promotes anti apoptotic activity in hematopoietic cells including B lymphocytes . ^^^ The TrkA ( mt / mt ) EB LCL derived from the CIPA patient and the TrkA ( wt / mt ) EB LCL derived from the carrier with the heterozygous TrkA mutation did not show any responses to NGF on anti apoptotic activity . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The effect of NGF was prevented by K 252a ( 100 nM ) , an inhibitor of TrkA autophosphorylation . ^^^ The results show that NGF selectively attenuated opioid mediated inhibition of 1 ( Ba ) via TrkA receptor activation , possibly by altering opioid receptor function . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
MATERIALS AND METHODS : We investigated the NGF , BDNF , GDNF and NGF receptors ( TrkA and p 75 ) expression in the tumour tissues , cerebrospinal fluid ( CSF ) and plasma of ten children affected by low grade astrocytomas and ependymomas . ^^^ Gene expression of NGF and its high affinity receptor ( TrkA ) are reduced in tumour tissues , whereas the number of cells immunopositive to the low affinity NGF receptor ( p 75 ) is increased . ^^^ CONCLUSION : Reduced expression of NGF and TrkA has been shown in low grade astrocytomas and ependymomas . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Neuronal differentiation and TrkA expression of neuroblastoma induced by the combination treatment of interferon gamma and NGF ] . ^^^ While there was no significant change of TrkA mRNA level in the NGF group ( P > 0 . 05 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The objective of the present report was to study the expression of the low affinity nerve growth factor ( NGF ) receptor p 75 and of the activated high affinity NGF receptor TrkA in malignant mesothelioma ( MM ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
ProNGF binds to the high affinity receptor , TrkA , as determined by cross linking to PC 12 cells , and is also slightly less active than mature NGF in promoting phosphorylation of TrkA and its downstream signaling effectors , Erk1 / 2 , in PC 12 and NIH3T3 TrkA cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
However , it is unclear whether the NGF high affinity receptor tyrosine kinase A ( TrkA ) and the NGF low affinity receptor p75NTR are altered in the state of sympathetic hyperinnervation in the heart . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
METHODS : Trk phosphorylation in response to exogenous NGF , BDNF , NT 3 , and NT 4 treatment was studied in LC cells and ONH astrocytes using immunoprecipitation and Western blotting . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To examine the role of nerve growth factor ( NGF ) in postoperative pain , we administered the tyrosine kinase A ( Trk A ) immunoglobulin G ( IgG ) fusion ( 1 to 10 mg / kg ) molecule before and after plantar incision . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To assess NTs in the NuGr in PN , mRNA expression of BDNF , nerve growth factor ( NGF ) , and NT receptors TrkA , TrkB , and p 75 was determined 1 week after ligation of L 5 and L 6 spinal nerves ( SNL ) . ^^^ TrkA , TrkB , and NGF mRNA levels decreased , whereas p 75 mRNA increased , in ipsilateral SNL NuGr compared with SHAM ; BDNF was undetectable . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Autophosphorylation of NGF receptor TrkA and activation of ERK1 / 2 after NGF treatment were scarcely detected in GM1+ cells . ^^^ However , dimer formation of TrkA upon NGF treatment was markedly suppressed in GM1+ cells in both cross linking analysis with Bis ( sulfosuccinimidyl ) suberate 3 and 125I NGF binding assay . ^^^ TrkA kinase activity was differentially regulated when GM 1 was added to the kinase assay system in vitro , suggesting suppressive / enhancing effects of GM 1 on NGF signals based on the concentration . ^^^ These results suggested that overexpressed GM 1 suppresses the differentiation signals mediated by NGF / TrkA by modulating the properties of the lipid raft and the intracellular localization of NGF receptors and relevant signaling molecules . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This study examined the effects of hypomorphic p 75 neurotrophin receptor ( p75NTR ) expression and high levels of nerve growth factor ( NGF ) on trkA phosphorylation and downstream activation of p44 / 42 mitogen activated protein kinase ( MAPK ) . ^^^ Levels of phosphorylated trkA are increased in p 75 ( / ) neurons compared with 129 / SvJ neurons , and these higher levels are maintained with continuous exposure to NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Human mast cells express G protein coupled receptors for the complement component C3a ( C3aR ) and high affinity nerve growth factor ( NGF ) receptor tyrosine kinase , TrkA . ^^^ We found that NGF caused tyrosine phosphorylation of TrkA , resulting in a sustained Ca ( 2+ ) mobilization , NFAT activation , extracellular signal regulated kinase ( ERK ) phosphorylation , and chemokine , macrophage inflammatory protein 1beta ( MIP 1beta ) production . ^^^ These data demonstrate that NGF caused tyrosine phosphorylation of TrkA to induce chemokine production in HMC 1 cells via a pathway that mainly depends on sustained Ca ( 2+ ) mobilization and NFAT activation . ^^^ Furthermore , C3a enhances NGF induced transcription factor activation and chemokine production via a G protein mediated pathway that does not involve TrkA phosphorylation . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Recent investigations point to Trk A , the high affinity receptor for nerve growth factor ( NGF ) , as a candidate for the site of the mutation that causes the disorder . ^^^ Functional NGF receptors , such as Trk A and the Trk family of tyrosine kinases , are essential for NGF signaling of human lymphocytes . ^^^ In these B cells , NGF failed to induce Trk A phosphorylation , cytoskeleton assembly , or MAP kinase activation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Activation of the high affinity neurotrophin receptor tropomyosin related kinase A ( TrkA ) by nerve growth factor ( NGF ) leads to phosphorylation of intracellular tyrosine residues of the receptor with subsequent activation of signaling pathways involved in neuronal survival such as the phosphoinositide 3 kinase ( PI 3 K ) / protein kinase B ( PKB / Akt ) pathway and the mitogen activated protein kinase ( MAPK ) cascade . ^^^ In the present study , we tested whether inhibition of protein tyrosine phosphatases ( PTP ) by orthovanadate could enhance tyrosine phosphorylation of TrkA thereby stimulating NGF like survival signaling in embryonic hippocampal neurons . ^^^ Inhibition of PTP enhanced TrkA phosphorylation also in the presence of NGF antibodies indicating that NGF binding to TrkA was not required for the effects of orthovanadate . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The rat monoclonal neuroantibody alphaD 11 is a potent antagonist that prevents the binding of nerve growth factor ( NGF ) to its tyrosine kinase A receptor ( TrkA ) in a variety of systems , most notably in two in vivo systems linked to crucial pathological states , such as Alzheimer ' s disease and HIV infection . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
By real time PCR and immunohistochemistry , stress exposed mice showed an up regulation of NGF and its low affinity receptor p75NTR ; the NGF high affinity receptor TrkA was moderately down regulated . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
While robust sensitization of noxious heat or capsaicin responses by NGF is observed in adult DRG neurons , responses to such stimuli in trkA positive neurons from early postnatal animals are not sensitized by NGF . ^^^ These observations suggest a developmental switch in signal transduction cascades linking trkA receptors to hyperalgesia during postnatal development and differences in the signaling pathways mediating bradykinin and NGF induced sensitization . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Although NGF is known to bind to and activate the receptor tyrosine kinase TrkA , many downstream targets of NGF signaling may be possibly phosphorylated by nonreceptor tyrosine kinases such as c Src and focal adhesion kinase ( FAK ) . 2 . ^^^ In the present study , exposure of TrkA overexpressing PC 12 cells to NGF is found to cause a rapid and sustained loss in the recovery of a subpopulation of nominally active FAK ( i . e . , being autophosphorylated on the positive site of regulation ) . 3 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Therefore , we suggest that after inflammation near the cell body , NGF synthesized within the nerve root and DRG induces BDNF expression through trkA receptors and intracellular ERK MAPK . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Compared to TrkA , the function of p75NTR in nerve growth factor ( NGF ) endocytosis is less clear , and it is unknown whether p75NTR by itself may internalize other neurotrophins besides NGF . ^^^ We directly compared TrkA and p75NTR for their ability to internalize NGF , and we also examined the endocytosis of iodinated brain derived neurotrophic factor ( BDNF ) and neurotrophin 3 ( NT 3 ) by p75NTR . ^^^ Cells expressing solely TrkA internalized NGF more efficiently than cells expressing p75NTR . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have now detected , by immunohistochemistry , beta 3 subunits in 82 % of small / medium and 67 % of large diameter sensory neurons in intact human dorsal root ganglia : 54 % of beta 3 small / medium neurons were NGF receptor trkA negative . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF effects on LTP were mediated by TrkA receptors . ^^^ Indeed , blockade of TrkA by monoclonal antibody prevented NGF from inducing LTD following HFS . ^^^ We found that NGF or blockade of NGF signalling by anti TrkA antibody did not change the amplitude of the LTD induced by LFS . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This interest is based on the observation that CBF neurons , which provide the major source of cholinergic innervation to the cerebral cortex and hippocampus , undergo selective and severe degeneration in advanced AD and that the survival of CBF neurons depends upon NGF and its receptors , namely , trkA and p75NTR . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
It activated NGF receptor , TrkA and its downstream signaling pathways in PC 12 and promoted the survival of neuronally differentiated PC 12 cells deprived of serum . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Neurotrophins , such as NGF and BDNF , activate Trk receptor tyrosine kinases through receptor dimerization at the cell surface followed by autophosphorylation and intracellular signaling . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To discriminate these effects we used two p75NTR receptor positive lines of cholinergic neuroblastoma cells , SN 56 and T 17 that are devoid of or express high affinity NGF ( TrkA ) receptors , respectively . cAMP and retinoic acid caused differentiation of both cell lines . ^^^ Data indicate that : ( 1 ) positive cholinotrophic effects of NGF required activation of both TrkA and p75NTR receptors ; ( 2 ) cAMP / RA evoked differentiation inhibited NGF effects mediated by TrkA receptors and activated its p75NTR dependent suppressing influences and ( 3 ) a differentiation evoked decrease of mitochondrial acetyl CoA and an elevation of mitochondrial Ca could augment impairment of cholinergic neurons by neurotoxic signals . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The process of neurite extension after activation of the TrkA tyrosine kinase receptor by nerve growth factor ( NGF ) involves complex signaling pathways . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The response to NGF ( nerve growth factor ) is strongly dependent on the trafficking of its receptor , TrkA . ^^^ However , information is still scarce about the role of the cellular localization of the TrkA co receptor , p75NTR ( where NTR is neurotrophin receptor ) , following stimulation by NGF . ^^^ We found that , after binding to NGF , p75NTR was co immunoprecipitated with TrkA and was transcytosed at the basolateral membrane . ^^^ Interestingly , TrkA specific stimulation by basolateral NGF loading also induced the TrkA p75NTR interaction and subsequent p75NTR transcytosis at the basolateral surface . ^^^ Moreover , specific stimulation of p75NTR by NGF activated TrkA and the MAPK ( mitogen activated protein kinase ) pathway . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Inhibitors of MAP kinase that block p 53 transactivation and inhibitors of TrkA receptor also abolished HDAC activation , indicating that deacetylation of p 53 is an NGF dependent post translational mechanism of p 53 activation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We constructed a nonviral vector for targeted gene transfer to cells expressing nerve growth factor ( NGF ) receptor TrkA . ^^^ The peptide activated signal transduction pathways of the NGF receptor TrkA in PC 12 cells and supported the survival of the cells after serum deprivation . ^^^ The peptide mediated gene expression was not affected in PC 12 cells by co incubation with a blocking antibody against the low affinity NGF receptor p 75 and was significantly enhanced in NIH3T3 cells stably transfected with TrkA cDNA , suggesting the involvement of the high affinity NGF receptor TrkA without the participation of p 75 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Previously , we developed a proteolytically stable small molecule peptidomimetic termed D 3 as a selective ligand of the extracellular domain of the TrkA receptor for the NGF . ^^^ Here , the in vivo efficacy of D 3 as a potential therapeutic for cholinergic neurons was tested in cognitively impaired aged rats , and we compared the consequence of partial TrkA activation ( D 3 ) versus full TrkA / p75 activation ( NGF ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
On the other hand , it is blocked by deprivation of endogenous NGF with antibodies to NGF and also by Trk inhibitor K252a , suggesting that endogenously produced NGF and the activation of Trk receptor are required for Sema4D action on DRG neurones . ^^^ These indicate that neurite outgrowth promoting actions of Sema4D are similar between DRG neurones and PC 12 cells , since NGF Trk signalling are required for these actions . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
OBJECTIVE : In the present study , the effect of NGF on tyrosine kinase receptor trkA and the capsaicin receptor TRPV 1 expression in airway specific vagal sensory neurons located in the jugular nodose ganglia complex ( JNC ) of mice was investigated . ^^^ METHODS : Using retrograde neuronal tracing in combination with double labelling immunohistochemistry , SP , trkA and TRPV 1 receptor expression was examined in airway specific sensory neurons of BALB / c mice before and after NGF treatment . ^^^ RESULTS : NGF injected into the lower airway was able to induce SP ( 13 . 0+ / 2 . 03 % vs . 5 . 9+ / 0 . 33 % ) and trkA expression ( 78+ / 2 . 66 % vs . 60+ / 2 . 11 % ) in larger diameter ( > 25 microm ) , capsaicin insensitive and trkA positive vagal sensory neurons that were retrograde labelled with Fast Blue dye from the main stem bronchi . ^^^ CONCLUSION : Based on the extent of SP and trkA co expression in airway specific neurons by NGF treatment , the present study suggests that , following a peripheral activation of trkA receptor on SP afferent by NGF which is elevated in allergic inflammation , there may be trkA mediated SP induction to mediate neurogenic airway inflammation . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The development of crural Pacinian corpuscles was explored in neonatal mutant mice lacking nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , neurotrophin 3 ( NT 3 ) or neurotrophin 4 ( NT 4 ) , or their cognate Trk receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Both the survival and proliferation of breast cancer cells are strongly stimulated by NGF , mediated by TrkA and p75NTR respectively , utilising signaling pathways similar to those described for neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Intradermal injection of capsaicin and NGF produce heat hyperalgesia by activating their respective TRPV 1 ( transient receptor potential vanilloid receptor 1 ) and TrkA receptors on nociceptor sensory nerve terminals . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA is a receptor tyrosine kinase activated primarily by nerve growth factor ( NGF ) to regulate differentiation , survival , and other important functions of neurons . ^^^ We show here that T . cruzi , via its neuraminidase , binds TrkA in a NGF inhibitable manner , induces TrkA autophosphorylation , and , through TrkA dependent mechanisms , triggers phosphatidylinositol 3 kinase ( PI3K ) / Akt kinase signaling , cell survival , and neurite outgrowth . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NB neuron survival is dependent on coexpression of the nerve growth factor ( NGF ) receptors p 75 ( NTR ) and TrkA , which bind NGF in cortical projection sites . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The nerve growth factor ( NGF ) receptor TrkA is widely expressed in non neural tissues suggesting pleiotropic functions outside the nervous system . ^^^ These data , confirmed in a classical reconstitution model using embryonic fetal liver from TrkA null mice , demonstrate that endogenous NGF modulates B cell development through TrkA in vivo . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immunocytochemical studies indicated that axons , which grow towards or away from localized NGF are TrkA positive , and TrkA / TG axons do not respond to any dose of NGF . ^^^ Collectively , our results suggest that localized sources of NGF can direct axon outgrowth from trigeminal ganglion in a dose and age dependent fashion , mediated by p75NTR signaling through TrkA expressing axons . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Using immunocytochemical methods , we examined the relationship between the upregulation of Na ( 5 ) 1 . 8 and the expression of the NGF receptors p 75 and TrkA in EAE . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
RESULTS : NGF and its TrkA receptor were expressed by normal rat cholangiocytes and up regulated following BDL . ^^^ In vitro , NGF and estrogens have an additive effect on cholangiocyte proliferation by acting on phosphorylated TrkA and p ERK1 / 2 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) , a neurotrophin required for the survival and maintenance of postganglionic sympathetic neurons , mediates its trophic effects by activation of its high affinity receptor trkA . ^^^ Null mutant mice lacking either NGF or trkA have profound sympathetic deficits , thus revealing the vital importance of NGF synthesis in target tissues and trkA expression by sympathetic neurons . ^^^ In this study , we sought to assess whether sympathetic neurons of the superior cervical ganglion ( SCG ) display alterations in their neurochemical phenotype in adult mice carrying one mutated allele for either NGF or trkA , and whether such differences result in altered patterns of innervation to the submandibular salivary gland and pineal gland . ^^^ In comparison with adult siblings , levels of trkA protein in the SCG were reduced in age matched NGF ( + / ) and trkA ( + / ) mice . ^^^ While NGF ( + / ) mice also had significantly fewer sympathetic axons innervating both the submandibular salivary gland and pineal gland , densities of sympathetic axons in both tissues reached normal levels in trkA ( + / ) mice . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We investigated the expression of four neurotrophins , nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , neurotrophin 3 ( NT 3 ) , and NT 4 , and five neurotrophin receptors , trkA , trkB , trkC , p 75 , and truncated trkB ( Trn B ) in single sensory neurons of the adult rat geniculate ganglion associated with the five innervation fields . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Finally , we show that FAIM interacts with both Trk and p 75 neurotrophin receptor NGF receptors in a ligand dependent manner . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Because SCN neurons do not express TrkA , NGF might have exerted its effects either through direct signalling of the neurons via p75NTR or by enhancing the activity of the cholinergic afferents to the SCN , which arise from the nucleus basalis magnocellularis ( NBM ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We investigated expression of NGF and its receptors , TrkA and p75NTR , in hepatocellular carcinomas ( HCCs ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Rat dorsal root ganglia ( DRG ) neurons were classified according to immunostaining for trk A and IB 4 and the effects of antibodies against NGF or GDNF on TRPV 1 expression within the groups were then analysed by immunohistochemical means . ^^^ Increased TRPV 1 expression within trk A positive neurons was prevented by anti NGF but not by anti GDNF , whereas TRPV 1 induction within the IB 4 positive group was blocked by anti GDNF but not by anti NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the cell culture model of nerve growth factor ( NGF ) deprived sympathetic neurons , we find that CEP 11004 induced a approximately 3 fold increase in the mRNA and protein levels of TrkA , the NGF receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This effect was mediated by specific binding of NGF to its receptor trk A , which was detected on all pancreatic cancer cells , with subsequent activation of the p44 / 42 MAPK signaling pathway . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) and brain derived neurotrophic factor were detected in myofibroblasts and neural cells , and both cell types expressed the NGF receptors trkA and p 75 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
These results are consistent with the recent experimental evidence that persistent tyrosine receptor kinase A ( TrkA ) activity is necessary to maintain transcription in the differentiating PC 12 cells ( Chang et al . 2003 ) and a sustained Src kinase activity is detected in response to NGF stimulation ( Gatti 2003 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
A significant correlation was observed between the severity of pruritus and protein gene product 9 . 5 immunoreactive intraepidermal nerve fibres , NGF immunoreactive keratinocytes , expression of Trk A in the epidermis and the density of immunoreactive vessels for E selectin . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA is essential components of the high affinity NGF receptor necessary to mediate biological effects of the neurotrophins NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In dexefaroxan treated devascularized rats , increases in NGF protein levels ( 2 fold ) and immunoreactivity were maintained in both the cortex and NbM over the entire 28 day postoperation period ; these increases were coincident with changes in functional markers characteristic of NGF ' s actions , including increases in choline acetyltransferase ( ChAT ) , p 75 and TrkA immunoreactivities , and a preservation of NbM cholinergic cell numbers . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In neural cells , nerve growth factor ( NGF ) initiates its survival signal through the binding to its cell surface receptor tyrosine kinase A ( TrkA ) . ^^^ In this study , we use the NGF TrkA specific interaction as a probe to identify TrkA on living PC 12 cell by atomic force microscopy ( AFM ) . ^^^ An NGF modified AFM tip was used to perform force volume ( FV ) imaging , generating a 2D force map to illustrate the distribution and association of TrkA on PC 12 cell membrane . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
MATERIALS AND METHODS : The bladder and MPG were used in immunohistochemical studies , enzyme linked immunoassays and Western blots for nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , TrkA and TrkB . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
RESULTS : Human monocytes express the neurotrophins NGF , BDNF and NT 3 but also their specific receptors TrkA , TrkB and TrkC . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Neutralization of NGF TrkA receptor interaction by the novel antagonistic anti TrkA monoclonal antibody MNAC 13 : a structural insight . ^^^ MNAC 13 , a mouse monoclonal antibody , recognizes with high affinity and specificity the neurotrophin receptor TrkA and displays a neutralizing activity toward the NGF / TrkA interaction . ^^^ Detailed knowledge of the molecular basis determining the specificity of this antibody is of importance because of its potential use as a modulator of the TrkA mediated NGF activity . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Treatment of PC 12 cells with buthionine sulfoximine ( BSO ) reduced the levels of GSH , a major cellular reductant , and enhanced NGF induced neuronal differentiation , activation of AP 1 and the NGF receptor tyrosine kinase , TrkA . ^^^ Consistent with the suppression , NAC inhibited NGF induced activation of TrkA , formation of receptor complexes comprising TrkA , Shc , Grb 2 , and Sos , and activation of phospholipase Cgamma and phosphatidylinositol 3 kinase . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Furthermore , this failure in differentiation correlated with significant attenuation in tyrosine phosphorylation of TrkA ( a marker for NGF induced differentiation ) and reduced the expression of neuronal markers , Hu antigen , and MAP 2 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Because NGF signals through the tyrosine kinase ( TrkA ) NGF receptor and / or the p75NTR receptor , we used rescue experiments with a PC 12 cell mutant lacking TrkA to show that NGF induced PPARgamma activation is dependent on TrkA activation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Expression of nerve growth factor ( NGF ) , and its receptors trkA and p 75 in ovaries of the cyclic golden hamster ( Mesocricetus auratus ) and the regulation of their production by luteinizing hormone . ^^^ In the present study , changes in localization of nerve growth factor ( NGF ) and its receptors , trkA and p 75 in the ovary were investigated during the estrous cycle of the golden hamster . ^^^ The effect of LH surge on changes in localization of NGF , trkA and p 75 in the ovary was also investigated . ^^^ NGF and its receptors trkA and p 75 were localized in oocytes , granulosa cells and theca cells of various stages of follicles throughout the estrous cycle . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The expression of ChAT , VAChT , as well as tropomyosin receptor kinase A ( TrkA ) NGF receptors and phospho TrK receptors was increased by nicotine in the hippocampus . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The TrkA and TrkB tyrosine kinases are members of the neurotrophin receptor family and mediate survival , differentiation , growth , and apoptosis of neurons in response to stimulation by their ligands , NGF and BDNF , respectively . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Transactivation occurs independently of the TrkA extracellular ligand , nerve growth factor ( NGF ) , through a signaling pathway that is distinct from that used in the transactivation of other receptor tyrosine kinases and has consequences distinct from those elicited by NGF at the plasma membrane . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Hereditary sensory and autonomic neuropathy type 4 ( HSAN 4 ) is caused by mutations in the tyrosin kinase A ( TrkA ) gene , encoding for the high affinity receptor of nerve growth factor ( NGF ) . ^^^ The NGF TrkA system is expressed in many endocrine glands . ^^^ Our findings emphasize the importance of NGF TrkA pathway in the physiology of the neuroendocrine system and its response to stress . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Again , in contrast with NGF or SCTM 41 cells , the primary Schwann cell effect was Trk tyrosine kinase independent . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
As their axons establish contact with peripheral targets such as the skin , the number of neurons expressing nNOS decrease that correspond to increased immunoreactivity for nerve growth factor ( NGF ) in the skin , and its high affinity receptor , tyrosine kinase A ( trkA ) in both skin and DRG neurons . ^^^ The roles of NO , NGF and its receptor trkA in DRG neurons during different stages of development are discussed . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We demonstrate that NGF depolarizes the membrane of PC 12 cells within a minute and by using transfected NIH 3T3 Trk and p 75 cells we show that both the high affinity NGF receptor p 140 ( trk ) and the low affinity NGF receptor or p 75 ( NGF ) may be involved in the depolarization . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We now show that AML 1 ETO expression up regulates the level of TRKA mRNA and protein in these cells and that AML 1 ETO expressing CD34+ hematopoietic cells grown in the presence of five early acting hematopoietic cytokines further proliferate in response to nerve growth factor ( NGF ) . ^^^ NGF , which is normally expressed by bone marrow stromal cells , could provide important proliferative or survival signals to AML 1 ETO expressing leukemic or preleukemic cells , and the NGF / TRKA signaling pathway may be a suitable target for therapeutic approaches to AML . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In pheochromocytoma 12 ( PC 12 ) cells and sympathetic neurons , nerve growth factor ( NGF ) engagement with the tropomyosin related tyrosine kinase ( TrkA ) receptor activates the serine / threonine kinase glycogen synthase kinase 3beta ( GSK3beta ) , enabling it to phosphorylate the microtubule associated protein 1B ( MAP1B ) . ^^^ We now show , using pharmacological inhibitor studies of PC 12 cells and sympathetic neurons in culture and in vitro kinase and activation assays , that the MAPK pathway , and not the PI3K pathway , links NGF engagement with the TrkA receptor to GSK3beta activation in PC 12 cells and sympathetic neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
When normal mybolasts were examined in vivo for expression of NGF receptors , p 75 ( NTR ) was detected on myoblasts but the high affinity NGF receptor , trk A , was not co expressed with p 75 ( NTR ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To address this question , we investigated , both at light and electron microscopic levels , the cellular distribution of immunoreactivity for NGF and its low affinity receptors , ( p 75 ) and its high affinity receptor ( TrkA ) in the thymus of patients with MG . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nanomolar concentrations of either 1NMPP1 or 1NaPP1 , derivatives of the general kinase inhibitor PP 1 , inhibit NGF and BDNF signaling in TrkA ( F592A ) and TrkB ( F616A ) neurons , respectively , while no such Trk inhibition is observed in wild type neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Differential endocytic sorting of p75NTR and TrkA in response to NGF : a role for late endosomes in TrkA trafficking . ^^^ NGF binds to two receptors , p75NTR and TrkA . ^^^ Both p75NTR and TrkA were internalized in response to NGF and colocalized with early endosomes . ^^^ However , surprisingly , the subsequent endosomal trafficking paths of both NGF receptors diverged : whereas p75NTR recycled back to the surface , TrkA moved to late endosomes and underwent lysosomal degradation . ^^^ By performing subcellular fractionations of NGF stimulated PC 12 cells , tyrosine phosphorylated TrkA was recovered in fractions corresponding to late endosomes . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immunolocalization of nerve growth factor ( NGF ) and its receptors ( TrkA and p75LNGFR ) in the reproductive organs of Shiba goats . ^^^ The objective of this study was to determine the immunolocalization of NGF and its receptors ( TrkA and p75LNGFR ) in the reproductive tract of the Japanese Shiba goats . ^^^ The results showed that NGF and its receptors ( TrkA and p75LNGFR ) were expressed in granulosa cells , theca cells , interstitial cells and lutein cells in ovaries . ^^^ Immunoreactions for NGF , TrkA and p75LNGFR were also detectable in epithelial cells and muscle cells of the ampulla and isthmus of the oviduct , and in epithelial cells and uterine glands of the uterus . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF , the TrkA ligand , blocked this increase . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Here we report that TID 1 associates with the Trk receptor tyrosine kinases and regulates nerve growth factor ( NGF ) induced neurite outgrowth in PC 12 derived nnr 5 cells . ^^^ Overexpression studies showed that both TID 1 ( L ) and TID 1 ( S ) significantly facilitated NGF induced neurite outgrowth in TrkA expressing nnr 5 cells possibly through a mechanism involving increased activation of mitogen activated protein kinase . ^^^ Consistently knockdown of endogenous TID 1 , mediated with specific short hairpin RNA , significantly reduced NGF induced neurite growth in nnr 5 TrkA cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We therefore evaluated the effects of hyperoxia on the expression of BDNF , NGF , and their corresponding high affinity receptors , TrkB and TrkA , respectively , in the lung of rat pups . ^^^ Furthermore , hyperoxic exposure increased the expression of TrkB in peribronchial smooth muscle but had no effect on the distribution of the specific NGF receptor TrkA . ^^^ However , there was no corresponding effect on NGF and TrkA receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In embryonic day ( E ) 15 rat trigeminal ganglion ( TG ) , NGF receptor TrkA is expressed by small diameter neurons , NT 3 receptor TrkC and BDNF receptor TrkB are expressed by large diameter neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To investigate the expression of NGF and its receptors , p 75 and TrkA , in early developing follicles ( mostly primordial , primary and secondary follicles ) , ten ovarian samples from adolescents / adults aged 13 39 and 33 ovaries from human fetuses aged 19 33 gestational weeks ( GW ) were obtained and immediately fixed or frozen . ^^^ Total RNA was extracted from the frozen ovarian samples , and the expression of NGF , TrkA and p 75 was investigated by RT PCR . ^^^ Immunocytochemical staining revealed the expression of NGF in granulosa cells ( GC ) and oocytes ; TrkA was mainly in oocytes and in GC in minority of the samples ; and p 75 was in some of the stroma cells from fetuses aged less than 22 GW . ^^^ Transcripts of NGF and TrkA were identified by RT PCR in all samples , while those for p 75 were detected only in ovarian samples from fetuses aged less than 22 GW . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Dysfunction of nerve growth factor ( NGF ) and its high ( TrkA ) and low ( p75NTR ) affinity receptors has been suggested to underlie the selective degeneration of the nucleus basalis ( NB ) cholinergic cortical projection neurons in end stage Alzheimer disease ( AD ) . ^^^ Moreover , there is a loss of cortical TrkA in the face of stable p75NTR and increased proNGF levels , the precursor molecule of mature NGF , in early AD . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Activation of the system was achieved by means of a hybrid receptor comprising the extracellular domain of the nerve growth factor ( NGF ) receptor TrkA , the cytoplasmic part of c Met and a C terminally fused blue fluorescent protein ( BFP ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Following exposure to 100 ng / ml NGF and increasing concentrations of thimerosal ( 1 nM 10 microM ) , we measured the activation of TrkA , MAPK , and PKC delta . ^^^ In controls , the activation of TrkA MAPK and PKC delta peaked after 5 min of exposure to NGF and then decreased but was still detectable at 60 min . ^^^ Concurrent exposure to increasing concentrations of thimerosal and NGF for 5 min resulted in a concentration dependent decrease in TrkA and MAPK phosphorylation , which was evident at 50 nM for TrkA and 100 nM for MAPK . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To test the hypothesis that trkA ( the high affinity NGF receptor ) is selectively expressed in nociceptive dorsal root ganglion ( DRG ) neurons , we examined the intensity of trkA immunoreactivity in single dye injected rat DRG neurons , the sensory receptor properties of which were identified in vivo with mechanical and thermal stimuli . ^^^ We provide the first evidence in single identified neurons that strong trkA expression in DRGs is restricted to nociceptive neurons , probably accounting for the profound influence of NGF on these neurons . ^^^ NGF can influence electrophysiological properties of DRG neurons , probably by binding to trkA . ^^^ These findings suggest that in Aalpha / beta nociceptors , influences of NGF on expression levels of Nav1 . 8 are related to , and perhaps limited by , expression levels of trkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
METHODS : Expression of NGF , trkA ( NGFR ) and p75NTR on human fibroblasts grown from conjunctival biopsies and incubated for 2 or 6 days with NGF were evaluated by immunofluorescence , RT PCR , flow cytometry and ELISA . ^^^ RESULTS : NGF induced the expression of p75NTR in the fibroblasts that constitutively expressed only trkA ( NGF ) and increased the migration of wounded fibroblasts , but not their proliferation and collagen production . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Thus , we tested the hypothesis that exposure to ethanol would affect NGF synthesis as well as expression of NGF receptor trkA in this cell population . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the present study , we aim to show that non adherent bone marrow cells ( BMCs ) express TrkA , the nerve growth factor ( NGF ) receptor , and that addition of NGF promotes the survival and neuronal commitment of BMC transplanted into the experimentally injured brain of littermates mice . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The NGF induced effect on cholinergic neurons was direct , requiring activation and signaling via TrkA receptors , which were immunohistochemically localized to the cholinergic neurons in the MS / DB . ^^^ TrkA receptors were absent in putative GABAergic MS / DB neurons , and blockade of TrkA signaling in these and other noncholinergic neurons had no effect on their firing activity after exposure to NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF and trkA receptors were identified by immunohistochemistry in all tissues examined . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
As a first step toward exploring this , we studied in murine back skin ( C57BL / 6 ) whether intradermally injected interleukin 1beta ( IL 1beta ) , tumor necrosis factor alpha ( TNF alpha ) , and interferon gamma ( IFN gamma ) altered the cutaneous immunoreactivity patterns of nerve growth factor ( NGF ) , brain derived neurotrophic factor ( BDNF ) , neurotrophin 3 ( NT 3 ) , neurotrophin 4 ( NT 4 ) , Trk A , Trk B , Trk C and p75NTR and their receptors ( TrkA , TrkB , TrkC , p75NTR ) on the protein level in situ . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Kindling , an experimental model of epileptogenesis , and activation induced synaptic reorganization are modulated by nerve growth factor ( NGF ) , but whether NGF acts via its high affinity receptor TrkA and / or the common neurotrophin receptor p75NTR is unknown . ^^^ We previously demonstrated , and confirmed in this study , that inhibition of NGF binding to both TrkA and p75NTR inhibited kindling and decreased kindling induced mossy fiber sprouting . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Pincher similarly mediates macroendocytosis for NGF ( TrkA ) and BDNF ( TrkB ) in both peripheral ( sympathetic ) and central ( hippocampal ) neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the latter circumstances , the administration of nerve growth factor ( NGF ) restored the synthesis and expression of those neuropeptides despite the absence of TrkA receptors in SCN neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In PC 12 cells , inhibition of Kalirin expression using antisense RNA decreased nerve growth factor ( NGF ) induced TrkA autophosphorylation and process extension . ^^^ Kalirin overexpression potentiated neurotrophin stimulated TrkA autophosphorylation and neurite outgrowth in PC 12 cells at a low concentration of NGF . ^^^ Furthermore , elevated Kalirin expression resulted in catalytic activation of TrkA , as demonstrated by in vitro kinase assays and increased NGF stimulated cellular activation of Rac , Mek , and CREB . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA , the high affinity receptor for nerve growth factor ( NGF ) , is essential for the development of nociceptive sensory and sympathetic neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
It has been reported that two types of NGF receptors , high affinity receptor , TrkA , and low affinity receptor , p75NGFR , play important roles in this process . ^^^ We investigated the expression of NGF receptors ( NGFRs : TrkA and p75NGFR ) mRNA in 56 human primary pancreatic cancers , using real time quantitative reverse transcription PCR . ^^^ Moreover , pancreatic cancer cell lines were used to validate if the effects of NGF on pancreatic cancer cell growth are dependent on the expression levels and the balance of TrkA and P 75 receptors . ^^^ It appears that in pancreatic cancer cells the growth effects of NGF depend on the expression levels and the ratio of TrkA and p75NGFR . ^^^ Conversely , we also found that elevated p75NGFR expression is associated with a favorable prognosis ; we demonstrated that NGF exerts both stimulatory and inhibitory effects on pancreatic cancers with the effect based on the expression levels and the ratio of TrkA and p75NGFR . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Because nerve growth factor ( NGF ) is known to protect neuronal cells from oxidative stress induced cell death , we examined the NGF Trk mediated intracellular signaling pathway in these transfectants . ^^^ In the wild and mutant PS 1 cDNA transfected cells , NGF did not elicit the autophosphorylation response of Trk , although their basal levels of tyrosine phosphorylation were higher than those of mock transfected cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Neurotrophin Tyrosine Receptor ( NTRK 1 ) encodes a receptor tyrosine kinase that is activated in response to NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) is the ligand for two unrelated cellular receptors , TrkA and p 75 ( NTR ) , and acts as a mediator in the development and maintenance of the mammalian nervous system . ^^^ However , co expression of these receptors leads to enhanced neuronal survival upon NGF stimulation , possibly through a ternary p 75 ( NTR ) 10 NGF 10 TrkA complex . ^^^ Molecular models of the 2 : 2 p 75 ( NTR ) 10 NGF complex based on these data are not consistent with the further assembly of either symmetric ( 2 : 2 : 2 ) or asymmetric ( 2 : 2 : 1 ) ternary p 75 ( NTR ) 10 NGF 10 TrkA complexes . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) promotes proliferation via its high affinity receptor ( TrkA ) . ^^^ However , if proNGF is involved or if NGF can also promote hair growth via TrkA is unclear . ^^^ By immunohistochemistry , NGF and TrkA are found in the proliferating compartments of the epidermis and hair follicle throughout the cycle . ^^^ Together , our findings suggest an anagen promoting or anagen supporting role for NGF / TrkA , and a catagen promoting role for proNGF / p75 interactions . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In this study we investigated the cell localization of the two main receptors for nerve growth factor ( NGF ) , TrkA and p75NTR , in the cow and pig ovary , using immunohistochemistry . ^^^ Taken together , these results suggest a possible direct role of NGF on oocytes expressing TrkA and p75NTR , in addition to the well known roles in other ovary functions . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
TrkA NGF receptor plays a role in the modulation of p75NTR expression . ^^^ The cellular response to nerve growth factor ( NGF ) is mediated by two structurally unrelated receptors , TrkA and p 75 neurotrophin receptor ( p75NTR ) , which have been shown to interact resulting in reciprocal modulation of function . ^^^ In this study , we have examined the modulation of p75NTR protein expression by specific TrkA autophosphorylation sites in the presence or absence of NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Application of NGF halved cell viability but this was reversed by K252a , the TrkA inhibitor . ^^^ These results confirmed the paradoxical cytotoxic effect of neurotrophic NGF via TrkA in PC 12 cells following serum deprivation . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Expression levels of the NGF receptor TrkA , and NGF induced increases in mRNAs for the immediate early genes ( IEGs ) c fos and NGF inducible ( NGFI ) genes NGFI A , NGFI B and NGFI C , were identical among subclones . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Using intrathecal antisense against the NGF receptor , receptor tyrosine kinase ( TrkA ) , we found NGF to act at the primary afferent nociceptor directly in the Sprague Dawley rat . ^^^ Inhibitors of the three major pathways for TrkA receptor signalling , extracellular signal related kinase ( ERK ) / mitogen activated protein kinase kinase ( MEK ) ( ERK / MEK ) , phosphatidylinositol 3 kinase ( PI3K ) , and phospholipase Cgamma ( PLCgamma ) all attenuate NGF induced hyperalgesia . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Our previous results showed that inhibition of protein tyrosine phosphatases ( PTP ) by orthovanadate is an appropriate strategy to mimic nerve growth factor ( NGF ) effects in neurons , including enhanced phosphorylation of TrkA , stimulation of downstream survival signaling pathways , and protection against apoptotic stress . ^^^ In primary neurons , such NO activated survival signaling involves NGF like effects , including enhanced phosphorylation of TrkA and activation of PI 3 K / Akt and MAPK pathways . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Because of the limited therapeutic applications of nerve growth factor ( NGF ) , there has been increasing focus on the development of pharmacological tools to bypass the requirement of NGF for the activation of the TrkA tyrosine kinase receptor neuronal survival pathway . ^^^ In this issue of Molecular Pharmacology , the work by Culmsee et al . ( p . 1006 ) shows that NGF independent activation of TrkA by protein tyrosine phosphatase ( PTP ) inhibitors is only achieved when accompanied by release of nitric oxide ( NO ) . ^^^ This work identifies the integration of the NO / cGMP / protein kinase G ( PKG ) and NGF / TrkA pathways to induce activation of Akt and ERK1 / 2 and mediate neuronal survival in the absence of NGF . ^^^ This Perspective comparatively reviews two major signal transduction pathways that mediate NGF independent neuronal survival by activating the TrkA pathway : the NO / cGMP / PKG and adenosine / G protein coupled receptor ( GPCR ) pathways . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF induced phosphorylation of TrkA and mitogen activated protein kinase was significantly diminished in the necdin null sensory ganglia . ^^^ These results suggest that paternally expressed necdin facilitates TrkA signaling to promote the survival of NGF dependent nociceptive neurons . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Transient exposure of the cells to 200 microM H2O2 triggered a significant reduction of cell viability and decreased the mRNA and protein levels of NGF , neurotrophin receptor P 75 ( P75NTR ) receptor and tyrosine kinase A ( TrkA ) receptor . ^^^ Incubation of cells with 10 microM huperzine A prior to H2O2 exposure significantly elevated their survival and restored the mRNA and protein levels of NGF , P75NTR receptor and TrkA receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To study the mechanism of the innoxious touch stimulus on the modulation of hyperalgesia and the expression of the C fos and the nerve growth factor ( NGF ) receptor TrkA in the spinal dorsal horn neurons following the chronic constriction injury ( CCI ) of the sciatic nerve in rats , 60 female Sprague Dawley rats were randomly divided into sham operation group and CCI group , with each group being further divided into 3 subgroups on the 7th , 14th and 28th day after operation ( n = 10 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) acts on the two receptor system of trkA and p 75 to mediate neuroprotection and influence phenotype and function in the peripheral nervous system , but the effects of NGF on the enteric nervous system ( ENS ) are virtually unknown . ^^^ To establish a basis for enteric responsiveness to NGF , we studied the presence and distribution of NGF sensitive receptors in the myenteric neurons of the normal rat colon and examined their activation via trkA phosphorylation . ^^^ Fluorescent immunocytochemistry on wholemounts showed that the two NGF receptors were abundantly present in the ENS , with 71 % of all neurons positive for trkA and 78 % for p 75 . ^^^ More thanr 60 % of the myenteric neurons expressed both receptors , and exogenous application of NGF resulted in trkA phosphorylation , evidence for high NGF sensitivity within the ENS . trkA was co expressed with choline acetyltransferase ( 61 % of trkA positive neurons ) , neuronal nitric oxide synthase ( 22 % ) , or calbindin ( 10 % ) , suggesting widespread potential for NGF action . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
It has been associated with mutations in the NTRK 1 gene , located in 1q21 22 and encoding a high affinity NGF receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We developed indirect ELISA methods for : choline acetyltransferase ( ChAT ) ; the vesicular acetylcholine transporter ( VAChT ) ; the high affinity choline transporter ( HACT / CHT ) ; TrkA , the high affinity NGF receptor ; the p 75 neurotrophin receptor ( p 75 ( NTR ) ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF caused dose dependent proliferation of HASMC and induced TrkA phosphorylation , both abolished by the tyrosine kinase inhibitor K252a . ^^^ In conclusion , NGF activation of the TrkA receptor involves two distinct signalling pathways : PKC selectively activates p 38 , and the ras / raf pathway selectively activates ERK1 / 2 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NF 1 encodes a GAP for the NGF receptor TrkA , and NF 1 mutations promote survival after NGF withdrawal . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF mediated stimulation of HAEC migration was completely blocked by the NGF / TrkA receptor antagonist K252a [ ( 8R * , 9S * , 11S * ) ( / ) 9 hydroxy 9 methoxycarbonyl 8 methyl 2 , 3 , 9 , 10 tetrahydro 8 , 11 epoxy 1H , 8H , 11H 2 , 7b , 11a triazadibenzo ( a , g ) cycloocta ( c , d , e ) trindene 1 one ] ( 30 nM ) but not by the VEGF / Flk receptor antagonist SU 5416 [ 3 [ ( 2 , 4 dimethylpyrrol 5 yl ) methylidenyl ] indolin 2 one ] ( 250 nM ) , indicating a direct effect of NGF via TrkA receptor activation on HAEC migration . ^^^ Viper NGF represents a novel pharmacological tool to investigate possible TrkA receptor subtypes in endothelial cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immunohistochemistry reveals that nerve growth factor ( NGF ) like immunoreactive ( LIR ) , tyrosine kinase ( trk ) A LIR , trkB LIR , and p 75 LIR elongated , differentiated taste cells are present within all lingual taste buds , whereas neither neurotrophin ( NT ) 3 nor trkC LIR was detected in taste cells . ^^^ NGF , pro NGF , and trkA coexist in type 2 taste cells , i . e . , those expressing phospholipase Cbeta 2 ( PLCbeta 2 ) . p 75 LIR also is present in both BDNF and NGF taste cell populations . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Tyrosine kinase A ( TrkA ) is an essential component of the high affinity nerve growth factor ( NGF ) receptor necessary to the mediate the biological effects of the neurotrophins , NGF . ^^^ Moreover , the postnatal development related increase in the expression of TrkA cells shows that NGF may have a trophic effect on these cerebral cortex neurons from the postnatal period . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The minimal 5 ' promoter was determined , and TrkA specific inhibitor K252a inhibited the NGF induced promoter activity of SPHK 1 . ^^^ These results suggest the signal transduction pathway from NGF receptor TrkA to transcription factor Sp 1 protein binding to the promoter Sp 1 like motif in NGF induced rat SPHK 1 gene expression . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
This study focuses on two other possible mechanisms for loss of trophic support : diminished release of NGF from hippocampal neurons or diminished TrkA receptor response of BFCNs to NGF . ^^^ Since cholinergic degeneration coupled with altered levels of NGF and TrkA receptors are also seen in human aging and AD , the loss of acute responsivity to NGF in the BFCNs may also play a role in these processes . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Congenital insensitivity to pain with anhidrosis ( CIPA ) is an autosomal recessive disorder caused by mutations in the neurotrophic tyrosine receptor kinase 1 ( NTRK 1 ) gene which encodes the receptor for nerve growth factor ( NGF ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Expression of nerve growth factor ( NGF ) , and its receptors TrkA and p 75 in the reproductive organs of the adult male rats . ^^^ Immunolocalization of nerve growth factor ( NGF ) and its receptors , TrkA and p 75 in the reproductive organs of adult male rats was investigated . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immunochemical methods were used to measure NGF , high ( TrkA and phospho TrkA ) and low ( p 75 neurotrophin receptor ) affinity NGF receptors , choline acetyltransferase ( ChAT ) , and the vesicular acetylcholine transporter ( VAChT ) in memory related brain regions . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
One rather unique aspect of the sensory innervation of bone , that may partially explain the analgesic efficacy of anti NGF therapy in relieving prostate cancer induced bone pain , is that nearly all nerve fibers that innervate the bone express trkA and p 75 , and these are the receptors through which NGF sensitizes and / or activates nociceptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
An autocrine loop involving NTRK 1 and NGF is associated with tumor progression in prostate carcinoma and in breast cancer . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Furthermore , cells transfected with chimeric TNFalpha / NGF receptors demonstrated that the simultaneous presence of both p75NTR and TrkA signaling is necessary to synergize with TNFalpha to mediate iNOS expression . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Localization of NGF and TrkA at mitotic apparatus in human glioma cell line U 251 . ^^^ It has previously been implicated that nerve growth factor ( NGF ) with its high affinity receptor tyrosine kinase A ( TrkA ) could play an important role in the growth modulation of human tumor cells , such as glioblastoma multiform cell lines and human breast cancer cell lines . ^^^ However , the direct mitogenic effects of NGF and TrkA in these tumor cells still remain to be elucidated . ^^^ Herein we show , by immunofluorescence staining , that NGF was colocalized with gamma tubulin at the centrosomes or the spindle poles throughout the cell cycle and phosphorylated TrkA was colocalized with alpha tubulin at mitotic spindle in the glioma cell line U 251 . ^^^ The results suggest that NGF concentrated to centrosome can recruit its receptor TrkA there and cause phosphorylation of the latter . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Tyrosine kinase A ( TrkA ) receptor blockade abolished NGF induced beta and gamma ENaC expression and neurite formation . ^^^ These data indicate NGF TrkA regulation of ENaC expression may be required for neurite growth and may suggest a novel role for DEG / ENaC proteins in neuronal remodeling and differentiation . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Effect of anti NGF on ovarian expression of alpha 1 and beta 2 adrenoceptors , TrkA , p75NTR , and tyrosine hydroxylase in rats with steroid induced polycystic ovaries . ^^^ Rat weight , estrous cyclicity , ovarian morphology , ovarian mRNA , and protein expression of alpha 1 AR subtypes , beta 2 AR , the NGF receptor tyrosine kinase A ( TrkA ) , p 75 neurotrophin receptor ( p75NTR ) , and tyrosine hydroxylase ( TH ) were analyzed . ^^^ Ovaries in both PCO and PCO anti NGF groups decreased in size as well as in number and size of corpora lutea . mRNA expression of alpha1a AR and TrkA in the ovaries was lower , whereas expression of alpha1b and alpha1d AR and TH was higher , in the PCO group than in controls . ^^^ Anti NGF treatment in the PCO group restored all changes in mRNA and protein content , except that of alpha1b AR and TrkA mRNAs , to control levels . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) binding to p 75 ( NTR ) influences TrkA signaling , yet the molecular mechanism is unknown . ^^^ We observe that NGF stimulates TrkA polyubiquitination , which was attenuated in p 75 ( / ) mouse brain . ^^^ NGF stimulated formation of a TrkA / p75 ( NTR ) complex through the p 62 scaffold , recruiting the E3 / TRAF6 and E2 / UbcH7 . ^^^ Peptide targeted to the TRAF 6 binding site present in p 62 blocked interaction with TRAF 6 and inhibited ubiquitination of TrkA , signaling , internalization , and NGF dependent neurite outgrowth . ^^^ Mutation of K 485 to R blocked TRAF 6 and NGF dependent polyubiquitination of TrkA , resulting in retention of the receptor on the membrane and an absence in activation of specific signaling pathways . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) contents in sciatic nerves and the expression of NGF receptor TrkA in DRGs were decreased . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In this study , we investigated alterations in the NGF pathway in keratoconus affected corneas and found a total absence of the NGF receptor TrkA ( TrkA ( NGFR ) ) expression and a decreased expression of NGF and p 75 ( NTR ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) and its receptor tyrosine kinase A ( TrkA ) participate in endocrine pancreas morphogenesis and insulin secretion in vitro . ^^^ CIPA suggests for the first time that the NGF TrkA pathway may play a role in insulin secretion in response to glucose challenge in humans . ^^^ Additional studies on the clinical significance of NGF TrkA effects on insulin secretion are required . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
One possibility is that the drug increases the expression of tyrosine kinase A ( TrkA ) nerve growth factor ( NGF ) receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Meanwhile , nerve growth factor ( NGF ) is critically involved in cell survival and neuroprotective effects via the extracellular signal related kinase ( ERK ) pathway or the phosphatidylinositol 3 kinase ( PI 3 K ) pathway mediated by the high affinity NGF receptor , tropomyosin related kinase A ( TrkA ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The functional effects of nerve growth factor ( NGF ) and its precursor , pro NGF , are thought to be mediated through binding of these ligands to one or both of their receptors , TrkA and p75NTR . ^^^ While the signaling pathways and downstream effects of NGF binding to TrkA are reasonably well known , those related to the binding of NGF and pro NGF to p75NTR are less well understood . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF mediated nuclear translocation of PIPSLS was blocked by K252a , a TrkA inhibitor , or wortmannin , a PI3K inhibitor . ^^^ These findings suggest that nuclear translocation of PIPS is involved in NGF mediated neuronal survival via TrkA , PI3K , and Gab 1 signaling pathway . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immunoblot analysis demonstrated that Cx 43 and the mitogen activated protein kinase ( MAPK ) , ERK 1 / 2 , were phosphorylated in response to TrkA activation via NGF and that phosphorylation could be prevented by treatment with the MEK 1 / 2 inhibitor U 0126 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) and its TrkA receptor exert important bioactivities on neuronal cells such as promoting survival and neurite outgrowth . ^^^ Inhibiting Rab 7 by expression of a green fluorescent protein tagged , dominant negative Rab 7 variant resulted in endosomal accumulation of TrkA and pronounced enhancement of TrkA signaling in response to limited stimulations with NGF , such as increased activation of Erk1 / 2 ( extracellular signal regulated kinase 1 / 2 ) , neurite outgrowth , and expression of GAP 43 ( growth associated protein 43 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The human parasite Trypanosoma cruzi , the agent of Chagas ' disease , expresses a membrane bound neuraminidase / trans sialidase , also known as parasite derived neurotrophic factor , PDNF , because it binds and activates nerve growth factor ( NGF ) receptor TrkA in neuronal cells . ^^^ Peptide Y 21 , therefore , reproduces several TrkA dependent activities of PDNF and NGF . ^^^ However , Y 21 inhibits the binding of PDNF but not NGF to TrkA . ^^^ These findings raise the possibility that Y 21 reacts with a TrkA site required for the binding of PDNF but not NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Here we show that NGF , acting on the TrkA receptor , activates a signalling pathway in which PI 3 kinase plays a crucial early role , with Src kinase as the downstream element which binds to and phosphorylates TRPV 1 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In chick retina , migratory RGCs express p 75 ( NTR ) , whereas layered RGCs express the high affinity NGF receptor TrkA , which may switch the pro apoptotic signaling of p 75 ( NTR ) into a neurotrophic one . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The expression of NGF is high in injured and inflamed tissues , and activation of the NGF receptor tyrosine kinase trkA on nociceptive neurons triggers and potentiates pain signalling by multiple mechanisms . ^^^ Several pharmaceutical companies have active drug discovery and development programs that are based on a variety of approaches to antagonise NGF , including NGF ' capture ' , blocking the binding of NGF to trkA and inhibiting trkA signalling . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NGF utilizes two receptors , the NGF specific tyrosine kinase receptor , TrkA , and also the non specific neurotrophin receptor , p 75 ( NTR ) ( p 75 ) . ^^^ Furthermore , when neurons were exposed to K252a , a relatively specific TrkA kinase inhibitor , the NGF effect on SP was also inhibited . ^^^ Our data suggest that NGF up regulation of SP expression requires the involvement of both TrkA and p 75 , although the specific contribution of each receptor to SP signaling remains to be determined . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the present study , we have investigated the expression profile of neurotrophins NGF , BDNF and NT 3 and their high affinity ( TrkA , TrkB , TrkC ) and common low affinity ( p75NTR ) receptors before and during neural differentiation of rat BMSCs by RT PCR . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We found that 2 1beta , but not NGF , promotes fibroblasts ' survival and that NGF stimulates trkA receptor expression , down regulates TFG alpha , and has no effect on TNF beta immunoreactivity . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
However , it is unknown whether human hair growth is also controlled through p75NTR , its high affinity ligand pro NGF , and / or the growth promoting high affinity NGF receptor tyrosine kinase A ( TrkA ) . ^^^ In microdissected human scalp anagen hair bulbs , mRNA for NGF , pro NGF , p75NTR , and TrkA was transcribed . ^^^ Immunohistomorphometry and in situ hybridization detected strong NGF and pro NGF expression in terminally differentiating inner root sheath keratinocytes , whereas TrkA was co expressed with p75NTR in basal and suprabasal outer root sheath keratinocytes . ^^^ During spontaneous catagen development of organ cultured human anagen hair follicles , p75NTR mRNA levels rose , and p75NTR and pro NGF immunoreactivity increased dramatically in involuting compartments primarily devoid of TrkA expression . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) contributes to the sympathetic sprouting , and NGF signaling starts with NGF stimulated autophosphorylation of TrkA , which is a high affinity receptor of NGF . ^^^ The effect of LAs on NGF stimulated TrkA activity was examined to analyze autophosphorylation of TrkA using immunoprecipitation and immunoblotting . ^^^ The inhibition of NGF stimulated tyrosine kinase activity of TrkA might be involved in the mechanisms of suppression of neurite outgrowth induced by LAs . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Experiments were conducted using female golden hamsters to identify the presence of nerve growth factor ( NGF ) and its receptors NTRK 1 and TNFRSF1B in the uteri of female animals and regulation on their expression by estrogen and progesterone . ^^^ NGF and its receptor NTRK 1 were immunolocalized to luminal epithelial cells , glandular cells , and stromal cells . ^^^ Strong immunostaining of NGF and its receptors NTRK 1 and TNFRSF1B was observed in uteri on the day of proestrus as compared to the other stages of the estrous cycle . ^^^ To clarify the effects of estrogen and progesterone on NGF , NTRK 1 , and TNFRSF1B expression , adult female golden hamsters were ovariectomized and treated with estradiol 17beta and / or progesterone . ^^^ Treatment with progesterone also increased NGF and NTRK 1 expression in the uterus . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Under normal conditions , expression of the p 75 neurotrophin receptor ( p75NTR ) by sympathetic neurons can increase the affinity of the signaling receptor , trkA , to target derived nerve growth factor ( NGF ) at distal axons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We further considered initial hints that Ang 1 induced neuritogenesis involves transactivation of the high affinity nerve growth factor ( NGF ) receptor trkA . ^^^ Likewise , neurite outgrowth was impaired in the presence of inactivating NGF antibodies as well as upon inhibition of the NGF high affinity trkA receptor with the antagonist K252a , indicating a tight cooperation of Ang 1 and NGF in the control of neuritogenesis . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In neurons , NGF occupancy of p 75 neurotrophin receptor ( p 75 ( NTR ) ) has been shown to promote neuronal apoptosis , while occupancy of tropomyosin receptor kinase A ( TrkA ) promotes survival of injured neurons . ^^^ In macrophages , recent results suggest that NGF via TrkA mediates resistance to cell death through the interaction with TLR 2 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The present findings suggest a role of the NGF / TrkA / p75 system in the physiology of reproduction , but the practical relevance of this remains to be established . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In all species studied NGF , TrK A and TrK C like immunoreactivity was observed in neurons and fibers of adrenal ganglia . ^^^ Double immunolabelings NGF / TrK A , NGF / TrK C and TrK A / TrK C showed colocalization in some neurons and fibers in adrenal ganglia . ^^^ In addition , NGF could be utilized by neuronal populations of adrenal ganglia through its preferential receptor TrK A by an autocrine or paracrine modality of action . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Crk , an effector of the nerve growth factor signaling pathway , delays apoptotic cell death in neurotrophin deprived PC 12 cells . 5 Crk is a member of a class of SH 2 and SH 3 containing adaptor proteins that have been implicated in regulating the TrkA receptor tyrosine kinase and potentiating Nerve Growth Factor ( NGF ) mediated neurite outgrowth in pheochromocytoma ( PC 12 ) cells ( Hempstead et al , Mol . ^^^ Given the fact that NGF induces both differentiation and survival by binding to TrkA , we examined the rate of apoptotic cell death elicited by NGF withdrawal in native , 5 Crk , and TrkA expressing PC 12 cells . ^^^ While more than 50 % of native PC 12 cells underwent apoptosis within 48 h of NGF withdrawal , the 5 Crk and TrkA expressing cells were much more resistant to apoptosis under these conditions , whereby approximately 70 and 95 % , respectively , of the cells were alive . ^^^ However , unlike native PC 12 cells , neither 5 Crk or TrkA expressing PC 12 cells exhibited a G 1 arrest when incubated for 2 weeks in NGF . ^^^ Thus , 5 Crk and TrkA may protect NGF deprived PC 12 by preventing cell cycle arrest and hence an aborted entry into a defective cell cycle . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immobilization depended on the phosphorylation of the TrkA NGF receptor . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Exposure of human GCs to NGF increased FSHR mRNA content within 18 h of treatment , and this effect was blocked by the trk tyrosine kinase blocker K 252a . ^^^ Results : In normal ovaries , NGF and trkA ( NGF ' s high affinity receptor ) were detected by immunohistochemistry in GCs of preantral and antral follicles . ^^^ NGF and trkA are also present in thecal cells of antral follicles . ^^^ Both freshly collected and cultured GCs contained immunoreactive NGF and trkA in addition to their respective mRNAs . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Survival of CBF neurons depends upon binding of nerve growth factor ( NGF ) with high affinity ( trkA ) and low affinity ( p 75 ( NTR ) ) neurotrophin receptors produced within CBF neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Immunohistochemical studies were done of trophic factors ( NGF and FGF 2 ) and neurotrophin receptors ( trkA and p 75 ) in spinal cord and motor cortical areas from anatomopathological cases of TSP / HAM . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Studies have indicated that nerve growth factor ( NGF ) and its high affinity receptor tyrosine kinase A ( TrkA ) may play a role in perineural invasion in several malignancies in which perineural invasion is observed . ^^^ The present study was conducted to investigate the expression of NGF and TrkA in salivary ACC and to examine the effects of NGF on adhesion , migration and invasion capacities of a salivary ACC cell line ( SACC 83 ) in vitro . ^^^ PATIENTS AND METHODS : Expression of NGF and TrkA was explored using immunohistochemistry in paraffin embedded tissues of 32 cases of salivary ACC . ^^^ RESULTS : In ACC specimens , 31 ( 96 . 9 % ) and 32 ( 100 % ) tumors showed immunoreactivity for NGF and TrkA respectively . ^^^ Significant correlations were found between NGF / TrkA expression levels and perineural invasion ( P < . 05 ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Furthermore , since mutations to the NGF receptor , TrkA , have been noted to alter the behaviour of PC 12 cells in response to NGF , a PC 12 subline that expresses a mutated TrkA receptor was utilized to illustrate that a Y785F mutation in the cytoplasmic tail of TrkA results in increased migration in response to the stimulus compared to the control PC12s . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Neurotrophins , mainly NGF and BDNF and their receptors ( LNTR , TrkA and TrkB ) are involved in these processes . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
RESULTS : Mural and cumulus granulosa cells were positive for BDNF , NT 4 / 5 , NT 3 , and NGF , as well as for Trk B , Trk C , and Trk A receptors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Moreover , ATPgammaS and NGF act synergistically to enhance neuronal survival through enhanced TrkA signaling . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Levels of TrkA receptor phosphorylation and downstream ERK activation induced by NGF were not influenced by GnT VB expression . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
In the current study we have identified STAT 3 as a novel signal transducer for TrkA , the receptor tyrosine kinase that mediates the functions of nerve growth factor ( NGF ) . ^^^ Activation of TrkA by NGF triggered STAT 3 phosphorylation at Ser 727 , and enhanced the DNA binding and transcriptional activities of STAT 3 . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Administration of LAR wedge Tat peptide to PC 12 cells resulted in increased proliferation , decreased cell death , increased neurite outgrowth , and augmented Trk PTK mediated responses to nerve growth factor ( NGF ) , a phenotype matching that found in PC 12 cells with reduced LAR levels . ^^^ The addition of LAR wedge peptide inhibited LAR co immunoprecipitation with TrkA , augmented NGF induced activation of TrkA , ERK , and AKT , and in the absence of exogenous NGF , induced activation of TrkA , ERK , and AKT . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Cellular localization of NGF and its receptors trkA and p75LNGFR in male reproductive organs of the Japanese monkey , Macaca fuscata fuscata . ^^^ Immunohistochemical methods were used in the present study to clarify distribution of nerve growth factor ( NGF ) and its receptors TrkA and p75LNGFR in excurrent ducts of the adult male Japanese monkey ( Macaca fuscata fuscata ) . ^^^ Leydig cells , Sertoli cells , and spermatogonia at various stages were positively stained for NGF , as well as for TrkA and p75LNGFR . ^^^ In the prostate , smooth muscle cells and basal cells were positively stained for NGF , TrkA , and p 75 LNGFR . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Lung eosinophils expressed the BDNF and NGF receptors tropomyosin related kinase ( Trk ) A and TrkB , and coculture with airway epithelial cells resulted in enhanced epithelial neurotrophin production , as well as in prolonged survival of eosinophils . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
BACKGROUND : We have previously shown that cultured human periodontal ligament ( HPL ) cells produce nerve growth factor ( NGF ) and express mRNA of tyrosine kinase receptor ( trkA ) , a high affinity receptor of NGF . ^^^ Endothelial cells also express NGF and trkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The NGF induced increase in NOX 1 mRNA was mediated by TrkA and accompanied by increased intracellular superoxide , which was suppressed by NADPH oxidase inhibitors . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Our data revealed that daily sessions of low frequency EA for 11 days to RCS rats during a critical developmental stage of retinal cell degeneration cause an increase of retinal nerve growth factor ( NGF ) and NGF high affinity receptor ( TrkA ) expression ; and increase of outer nuclear layer ( ONL ) thickness ; and enhanced vascularization . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We demonstrate that FRS 3 binds all neurotrophin Trk receptor tyrosine kinases and becomes tyrosine phosphorylated in response to NGF , BDNF , NT 3 and FGF stimulation in transfected cells and / or primary cortical neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
To further explore details of this mechanism , the expression of nerve growth factor ( NGF ) , production of which is induced by inflammatory cells and of the NGF receptor TrkA was examined in the PNS and the dorsal root ganglion using immunohistochemistry and a ribonuclease protection assay . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The activation of MAPK / Erk through the TrkA NGF signaling pathway is critical for growth and survival of neuronal cells . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
We have identified an E 3 ubiquitin ligase , Nedd 4 2 , that associates with the TrkA receptor and is phosphorylated upon NGF binding . ^^^ Activated TrkA receptor levels and the survival of NGF dependent sensory neurons , but not BDNF dependent sensory neurons , are directly influenced by Nedd 4 2 expression . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
It appears that the growth of pancreatic cancer cells stimulated by NGF depended on the expression levels and the ratio of TrkA to p75NGFR . ^^^ We demonstrated that NGF exerts both stimulatory and inhibitory effects on pancreatic cancers , with the overall effect determined by the expression levels and the ratio of TrkA to p75NGFR . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Studies showing that neurotrophin binding to p75NTR can promote cell survival in the absence of Trk ( tropomyosin related kinase ) receptors , together with recent structural data indicating that NGF may bind to p75NTR in a monovalent manner , raise the possibility that small molecule p75NTR ligands that positively regulate survival might be found . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
OBJECTIVE : To determine the expression of nerve growth factor ( NGF ) , tyrosine kinase receptor A ( trkA ) , and pan neurotrophin receptor ( p 75 ) in the lung tissues in asthmatic rats , and to explore their effects on the airway inflammation . ^^^ Not only the expression of NGF mRNA , but also its receptors trkA and p 75 mRNA in the lung tissues were significantly higher in the asthma group than those in the control group ( All P < 0 . 01 ) . ^^^ NGF can upregulate the expressions of p 75 and trkA mRNA in asthmatic rats , and then may promote their role in the airway neuronal inflammation in asthma . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Interestingly in the cornea , where NGF , trkA ( NGFR ) and p 75 ( NTR ) are expressed by epithelial cells and keratocytes , the NGF eye drop induces the healing of neurotrophic or autoimmune corneal ulcers . ^^^ NGF , trkA ( NGFR ) and p 75 ( NTR ) were found expressed by fibroblastic keratocytes . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The immunoreactivity of c Fos , NGF and its receptor TrkA after open field exposure in the central and medial nuclei of the rat amygdala . ^^^ The immunoreactivity ( ir ) of c Fos , NGF and its receptor , TrkA , following acute and chronic open field stress were studied in the CeA and MeA nuclei of the amygdala . ^^^ The brains were stained with the use of immunohistochemical methods for c Fos , NGF or TrkA . ^^^ In the control rats c Fos , TrkA and NGF ir cells were observed in the nuclei studied , but the quantity varied , being moderate or high ( immunoreactive to TrkA and NGF ) or low ( immunoreactive to c Fos ) . ^^^ In the animals exposed to acute open field stress the number of c Fos ir , NGF ir and TrkA ir cells in the nuclei under examination was differentiated but higher than that in the control animals . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Light and electron microscopy immunohistochemistry showed that human tonsillar samples were positive for all analyzed neurotrophins ( NGF , BDNF and NT 3 ) and their high affinity receptors ( TrkA , TrkB and TrkC , respectively ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Nerve growth factor ( NGF ) mimics play an important role for therapies that target the receptor tyrosine kinase A ( trkA ) . ^^^ The N terminal fragment of the NGF ( N term @ NGF ) was previously demonstrated to be an important determinant for affinity and specificity in the binding to trkA . ^^^ Molecular dynamics simulations are then used to investigate the stability of complexes between trkA and peptides mimicking N term @ NGF . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Like the index member of the Trk receptor ligand family , nerve growth factor ( NGF ) , PACAP promotes the differentiation of PC 12 cells , a well established cell culture model , to investigate neuronal differentiation , survival and function . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The compound induced sustained extracellular signal regulated kinase ( ERK ) activation that is crucial for neurite outgrowth activity without activating NGF receptor , TrkA . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Binding to isolectin B 4 ( IB 4 ) and expression of tyrosine kinase A ( trkA ) ( the high affinity NGF receptor ) have been used to define two different subgroups of nociceptive small dorsal root ganglion ( DRG ) neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Most biological actions of NGF and VEGF are mediated by their cognate receptor protein tyrosine kinases , tropomyosin related kinase ( trkA for NGF ) and kinase insert domain containing receptor ( KDR , VEGFR 2 , flk 1 for VEGF ) , which activate a complex and integrated network of signaling pathways in neurons and endothelial cells . ^^^ Two small molecules , K252a and SU 5416 , which are antagonists of trkA and VEGFR 2 , respectively , may serve as key tools in dissecting the role of NGF and VEGF in angiogenesis and neurogenesis . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Neutral glycosphingolipids are resident in membrane lipid rafts where high affinity nerve growth factor ( NGF ) receptor , Trk is co localized . ^^^ The results strongly suggest that these antibodies enhance NGF induced Trk autophosphorylation and neurite outgrowth as well as neurofilament M expression . ^^^ These data strongly indicate that these anti neutral glycosphingolipids antibodies have a functional impact on NGF Trk mediated intracellular signal transduction pathway . . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
BDNF , through p75NTR , promotes apoptosis and inhibits axonal growth of sympathetic neurons , antagonizing the pro survival and axon growth promoting actions of NGF through TrkA . ^^^ While the trafficking of the TrkA : NGF complex is well characterized , little is known about p75NTR : BDNF trafficking in these neurons . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
Biochemical studies have shown that domain 5 of the TrkA ( tropomyosin receptor kinase A ) receptor is involved in the binding of NGF ( nerve growth factor ) . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
The mouse NGF induced angiogenic effect was blocked by 1 microM K252a ( 1 . 149 + / 0 . 018 , p < . 001 ) , an antagonist of the NGF / trkA receptor , but not by 1 microM SU 5416 ( 1 . 263 + / 0 . 029 , p < . 001 ) , the VEGF / Flk1 receptor antagonist , indicating a direct , selective angiogenic effect of NGF via quail embryo trkA receptor activation . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
BACKGROUND : Nerve growth factor ( NGF ) and its high affinity receptor , tyrosine kinase A ( TrkA ) , are members of the neurotrophin family . ^^^ NGF TrkA are involved in murine hair morphogenesis and cycling . ^^^ In this investigation , we hypothesize that NGF TrkA proteins are expressed in the human scalp skin . ^^^ Moreover , NGF TrkA expression in HF changes with the transitions from anagen > > catagen > > telogen stages . ^^^ MATERIALS AND METHODS : To test our hypothesis and to fill this existing gap in literature , the immunostaining values ( semiquantitative evaluation of protein expression : SI , staining intensity ; PP , percentage of positive cells ; and IR score , immunoreactivity score ) of NGF and TrkA proteins were examined in human scalp skin by immunofluorescent and immunoperoxidase staining methods . ^^^ |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
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SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
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SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
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SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
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SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
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SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
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SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P01138 and P04629 |
Pubmed |
SVM Score :0.0 |
NA |
|