Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.61457877
Glial cell line derived neurotrophic factor ( GDNF ) has recently been shown to signal by binding to GDNF receptor alpha ( GDNFR alpha ) , after which the GDNF GDNFR alpha associates with and activates the tyrosine kinase receptor Ret . 0.61457877^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.90243112
In cells lacking RET , GDNF binds with high affinity to the NCAM and GFRalpha 1 complex , which activates Fyn and FAK . . 0.90243112^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :1.0901029
We have exploited sequence and functional divergences between the ectodomains of mammalian and amphibian RET molecules to map binding determinants in the human RETECD responsible for its interaction with the GDNF GFR alpha 1 complex by homologue scanning mutagenesis . 1.0901029^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :1.828797
In vitro binding experiments with soluble forms of RET , RETL 1 and RETL 2 demonstrate that while RETL 1 binds GDNF tightly to form a membrane associated complex which can then interact with RET , RETL 2 only forms a high affinity complex with GDNF in the presence of RET . 1.828797^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
To study the roles of GDNF in the regulation of tooth innervation and formation , we analyzed by in situ hybridization the expression patterns of GDNF and its receptors Ret , GDNF family receptor alpha 1 ( GFRalpha 1 ) , and GFRalpha 2 from the initiation of first molar formation to the completion of crown morphogenesis . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
RET activation may be mediated by a ligand complex comprising glial cell line derived neurotrophic factor ( GDNF ) and GDNF family receptor alpha 1 ( GFR alpha 1 ) . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Glial cell line derived neurotrophic factor ( GDNF ) signals through a receptor complex composed of the Ret tyrosine kinase and a glycosylphosphatidylinositol ( GPI ) anchored cell surface coreceptor , either GDNF family receptor alpha 1 ( GFR alpha 1 ) or GFR alpha 2 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
We investigated the presence of mutations in another member of the RET signalling complex , GDNF family receptor alpha 1 ( GFR alpha 1 ) , in a panel of 269 independent cases of HSCR . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
We investigated ligand receptor interactions in the glial cell line derived neurotrophic factor ( GDNF ) receptor complex , formed by the c Ret receptor tyrosine kinase and the glycosylphosphatidylinositol ( GPI ) anchored subunit GDNF family receptor alpha 1 ( GFRalpha 1 ) . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Recent studies have identified a multi component receptor system for the neurotrophic factor , glial cell line derived neurotrophic factor ( GDNF ) and its homolog , neurturin ( NTN ) , comprising the signaling tyrosine kinase , Ret and multiple GPI linked binding proteins , GDNF family receptor alpha 1 and alpha 2 ( GFRalpha 1 and GFRalpha 2 ) . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
We have cloned a partial cDNA of chicken glial cell line derived neurotrophic factor ( GDNF ) and systematically examined its expression pattern as well as that of GDNF binding components ( GDNF family receptor alpha 1 and 2 : GFRalpha 1 and 2 ) and a common signal transduction receptor ( c ret protooncogene : RET ) during very early developmental stages . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The RET proto oncogene encodes a receptor tyrosine kinase activated by the binding of factors from the glial cell line derived neurotrophic factor ( GDNF ) family to receptor alpha components such as GDNF family receptor alpha 1 ( GFR alpha 1 ) . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The biological effects of GDNF are mediated by GDNF family receptor alpha 1 ( GFRalpha 1 ) and c Ret . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The localization of mRNAs corresponding to the two components of the GDNF receptor , GDNF family receptor alpha 1 ( GFRalpha 1 ) and Ret , were demonstrated in adult adrenal medullary ganglion cells . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The authors studied the relation between perineural invasion in patients with bile duct carcinoma and the expression of glial cell line derived neurotrophic factor ( GDNF ) , GDNF family receptor alpha 1 ( GFRalpha 1 ) , and RET receptor tyrosine kinase , which are expressed in both central and peripheral nerve tissues . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The formation of the enteric nervous system ( ENS ) from neural crest derived cell precursors requires the growth factor glial cell line derived neurotrophic factor ( GDNF ) and the receptors Ret and GDNF family receptor alpha 1 ( GFRalpha 1 ) . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The signalling receptor complex for GDNF includes a dimer of Ret receptor tyrosine kinase and two molecules of GDNF family receptor alpha 1 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Hippocampal neurons express glial cell line derived neurotrophic factor ( GDNF ) , its receptors c Ret and the lipid anchored GDNF family receptor alpha 1 ( GFRalpha 1 ) , and the FGF receptor 1 ( FGFR 1 ) . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
About 50 , 20 , and 20 % of DRG neurons expressed GDNF family receptor alpha 1 ( GFR alpha 1 ) , GFR alpha 2 , and GFR alpha 3 mRNAs , respectively , and most of these neurons were positive to c ret mRNA . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The signaling receptor complex for GDNF typically includes both GDNF family receptor alpha 1 ( GFRalpha 1 ) and Ret receptor tyrosine kinase . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The biological actions of GDNF are mediated by a two receptor complex consisting of a glycosylphosphatidylinositol linked cell surface molecule , the GDNF family receptor alpha 1 ( GFRalpha 1 ) , and receptor protein tyrosine kinase Ret . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Glial cell line derived neurotrophic factor ( GDNF ) signals through multisubunit receptor complex consisting of RET tyrosine kinase and a glycosylphosphatidylinositol anchored coreceptor called GDNF family receptor alpha 1 ( GFRalpha 1 ) . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The glial cell line derived neurotrophic factor ( GDNF ) ligand activates the Ret receptor through the assembly of a multiprotein complex , including the GDNF family receptor alpha 1 ( GFRalpha 1 ) molecule . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
METHODS : Immunohistochemical assessment of GDNF , neurturin , persephin , artemin , GDNF family receptor alpha 1 and alpha 2 , and RET was performed for 51 cases of surgically resected pancreatic cancer . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Expression of the glial cell line derived neurotrophic factor ( GDNF ) receptors RET and GDNF family receptor alpha 1 ( GFRalpha 1 ) in human pancreatic cancer cells was determined by Western blot , immunofluorescence , and flow cytometry . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
We further demonstrate that GDNF promotes the formation of a physical complex between GDNFR alpha and the orphan tyrosin kinase receptor Ret , thereby inducing its tyrosine phosphorylation . ^^^ These findings support the hypothesis that GDNF uses a multi subunit receptor system in which GDNFR alpha and Ret function as the ligand binding and signalling components , respectively . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GDNF induced activation of the ret protein tyrosine kinase is mediated by GDNFR alpha , a novel receptor for GDNF . ^^^ GDNFR alpha binds GDNF specifically and mediates activation of the Ret protein tyrosine kinase ( PTK ) . ^^^ Treatment of Neuro 2a cells expressing GDNFR alpha with GDNF rapidly stimulates Ret autophosphorylation . ^^^ Ret is also activated by treatment with a combination of GDNF and soluble GDNFR alpha in cells lacking GDNFR alpha , and this effect is blocked by a soluble Ret Fc fusion protein . ^^^ A model for the stepwise formation of a GDNF signal transducing complex including GDNF , GDNFR alpha , and the Ret PTK is proposed . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Glial cell line derived neurotrophic factor ( GDNF ) , the most potent trophic factor yet described for both dopaminergic neurons of the substantia nigra and spinal motorneurons , has recently been shown to signal through a multireceptor complex composed of a novel glycosylphosphatidylinositol anchored GDNF receptor alpha ( GDNFR alpha ) and the receptor tyrosine kinase product of the c ret proto oncogene ( RET ) . ^^^ Importantly , we also see expression of RET mRNA in cellular populations within the cerebellum and the glomerular layer of the olfactory bulb , as well as in the subthalamic nucleus , which lack GDNFR alpha expression , indicating that RET functions either independently of GDNFR alpha or with GDNFR alpha presented in trans . ^^^ Conversely , GDNFR alpha is widely expressed in many regions in which RET expression is absent , suggesting that GDNFR alpha may associate with additional signaling receptors . ^^^ Finally , RET and GDNFR alpha show distinct patterns of regulated expression in the brain after kainic acid stimulation and in the sciatic nerve after nerve transection . ^^^ Taken together these findings indicate that GDNF , RET , and GDNFR alpha utilize multiple mechanisms to comprise physiologically relevant trophic circuits for different neuronal populations . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
A receptor complex comprised of TrnR 1 ( GDNFR alpha ) and Ret was recently identified and found to be capable of mediating both GDNF and NTN signaling . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GDNF mediates its actions through a multicomponent receptor system composed of a ligand binding glycosyl phosphatidylinositol ( GPI ) linked protein ( designated GDNFR alpha ) and the transmembrane protein tyrosine kinase Ret . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Expression of the RET receptor tyrosine kinase and GDNFR alpha in normal and leukemic human hematopoietic cells and stromal cells of the bone marrow microenvironment . ^^^ The RET proto oncogene product is a receptor tyrosine kinase representing the signal transducing molecule of a multisubunit surface receptor complex for the glial cell line derived neurotrophic factor ( GDNF ) , in which a novel glycosyl phosphatidylinositol ( PI ) linked protein ( termed GDNFR alpha ) acts as the ligand binding component . ^^^ We have analyzed expression of RET and GDNFR alpha in purified normal hematolymphopoietic cells , leukemia / lymphoma cell lines , and 154 primary samples from patients with hematopoietic malignancies encompassing different lineages and differentiation stages . ^^^ RET broad detection in primary tumors was not paralleled by the mutual expression of GDNFR alpha , which was detected only in 2 isolated primary samples and in 3 leukemia / lymphoma cell lines . ^^^ However , GDNFR alpha transcripts , in the absence of RET mRNA , were found in normal bone marrow stromal cells ( BMSC ) , in BM fibroblasts , and in two osteoblast cell lines previously described to support normal hematopoiesis . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Glial cell line derived neurotrophic factor ( GDNF ) and its receptor molecule GDNFR alpha , have recently been identified as members of the RET ligand binding complex . ^^^ Therefore , the genes encoding both GDNF and GDNFR alpha are excellent candidates for a role in the pathogenesis of those MEN 2 families and sporadic neuroendocrine tumors without RET mutations . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
In situ hybridization was then used to map cellular expression of the GDNF related trophic factor neurturin ( NTN ) and GDNFR beta mRNA in developing and adult mice , and comparisons with GDNFR alpha and RET were made . ^^^ NTN colocalized with RET and GDNFR alpha in ureteric buds of the developing kidney . ^^^ Although NTN and GDNFR beta expression patterns are sometimes complementary , this is not always the case , suggesting multiple modi operandi of GDNF and NTN in relation to RET and the two binding proteins , GDNFR alpha and GDNFR beta . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Ret expressing neurons also express the glycosyl phosphatidyl inositol linked ( GPI linked ) GDNF binding component GDNFR alpha and retrogradely transport 125I GDNF , indicating the presence of a biologically active GDNF receptor complex . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GDNF signals through a receptor complex consisting of the receptor tyrosine kinase Ret and a glycosyl phosphatidylinositol ( GPI ) linked receptor termed GDNFR alpha . ^^^ By using microinjection to introduce expression plasmids into neurons , we show that coexpression of NTNR alpha with Ret confers a survival response to neurturin but not GDNF , and that coexpression of GDNFR alpha with Ret confers a survival response to GDNF but not neurturin . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Another divergent member of the TGF beta family , GDNF , signals through Ret , a tyrosine kinase receptor ; binding to Ret requires the cooperation of GDNFR alpha . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Differential regulation of mRNAs for GDNF and its receptors Ret and GDNFR alpha after sciatic nerve lesion in the mouse . ^^^ This receptor is composed of a ligand binding subunit , called GDNF receptor alpha ( GDNFR alpha ) , and a signalling tyrosine kinase subunit , Ret . ^^^ Analysis of expression in muscle , nerve and spinal cord by RNase protection assay and in situ hydridization revealed that , in adult non lesioned mice , GDNF mRNA was expressed in the nerve and GDNFR alpha mRNA in the nerve and the spinal cord , while the expression of Ret was restricted to spinal cord motor neurons . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
More conclusive evidence showing that activation of GDNFR alpha by glial cell line derived neurotrophic factor induces phosphorylation of ret has confirmed ret as a signalling protein for glial cell line derived neurotrophic factor . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GDNF and its receptor complex of c RET tyrosine kinase and a glycosyl phosphatidylinositol linked protein GDNFR alpha are of great interest due to their potential use in the therapy of Parkinson ' s and motoneuron diseases . ^^^ Similarly to GDNFR alpha , GDNFR beta mediates GDNF induced Ret autophosphorylation in transfected cells . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Signal transduction of GDNF is mediated by binding to a glycosyl phosphatidylinositol ( GPI ) linked receptor GDNFR alpha and activation of c RET tyrosine kinase . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GDNF binds to GDNFR alpha and this complex , in turn , is believed to interact with the RET receptor tyrosine kinase to effect downstream signalling . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The actions of GDNF are mediated by a multicomponent receptor complex composed of the tyrosine kinase product of c ret and the ligand binding protein GDNF receptor alpha ( GDNFR alpha ) . ^^^ As reported previously , GDNFR alpha and c ret mRNA are present in the substantia nigra and ventral tegmental area , regions containing GDNF responsive dopamine neurons . ^^^ In areas rostral to the substantia nigra , c ret mRNA is not detected , whereas GDNFR alpha is found in numerous brain structures , including the hippocampus , cortex , medial geniculate , and the medial habenula , the latter area expressing the highest levels of GDNFR alpha mRNA in brain . ^^^ These results provide evidence that c ret and GDNFR alpha mRNA are expressed in neuronal populations involved in motor function and provides further support for GDNF as a target derived neurotrophic for these motor neurons . ^^^ The observation that GDNFR alpha mRNA is localized in several brain structures that do not contain detectable levels of c ret mRNA indicates that either GDNFR alpha utilizes signal transduction molecules other than c ret in these areas or that other GDNF like ligands that utilize GDNFR alpha as a receptor may be present . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GDNF transmits its signal primarily through a receptor complex containing the receptor tyrosine kinase Ret and a glycosyl phosphatidylinositol ( GPI ) linked receptor , GDNFR alpha . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Recently , GDNF and GFRA 1 ( GDNF family receptor , also known as GDNFR alpha ) , its GPI linked coreceptor , were demonstrated to be components of a functional ligand for RET . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
In this study , we assessed the expression levels of neurotrophin mRNAs and GDNF mRNAs and their receptor mRNAs for p 75 , TrkA , TrkB , TrkC , GDNFR alpha and Ret in the sural nerve biopsy specimens from various human neuropathies . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Up regulation of GDNFR alpha and c ret mRNA in facial motor neurons following facial nerve injury in the rat . ^^^ Glial cell line derived neurotrophic factor ( GDNF ) , a powerful trophic factor for developing , and injured adult motor neurons , has recently been shown to mediate its physiological effects via a multi component receptor system comprising the GDNFR alpha binding protein and the c ret receptor tyrosine kinase . ^^^ Using in situ hybridization histochemistry this study investigated whether adult motor neurons express mRNAs encoding GDNFR alpha and c ret , and explored possible time dependent changes in these mRNA species following facial nerve resection and crush injury . ^^^ The gradual return of c ret and GDNFR alpha mRNAs to control levels 21 days after facial nerve crush , parallels the axonal regeneration process , while nerve damage by resection has more severe consequences compared to nerve crush , reflected by the prolonged time course of increased GDNFR alpha mRNA , similar to markers such as the NGF receptor , galanin and GAP 43 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Mutational analysis of the GDNF / RET GDNFR alpha signaling complex in a kindred with vesicoureteral reflux . ^^^ Glial cell line derived neurotrophic factor ( GDNF ) mediates signaling across the cell membrane by interaction with the RET GDNFR alpha receptor complex . ^^^ Knowledge that mutations in the RET proto oncogene cause MTC and studies documenting genitourinary abnormalities in RET or GDNF knockout mice led us to examine the GDNF / RET GDNFR alpha signaling complex in this family . ^^^ Mutation abnormalities in the GDNF / RET GDNFR alpha signaling system do not cause VUR in this family . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Recently , glial cell line derived neurotrophic factor ( GDNF ) and a second family member , neurturin ( NTN ) , have been found to mediate their signals by binding to a heterotetrameric complex of c Ret tyrosine kinase receptors and glycosylphosphatidylinositol linked proteins , GFR alpha 1 ( GDNFR alpha ) or GFR alpha 2 ( TrnR2 / GDNFR beta / NTNR alpha / RETL2 ) . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
To ascertain whether the biological effects of ret mutations are modulated by GDNF , we have investigated the responsiveness to GDNF of ret mutants in cell lines coexpressing GDNFR alpha and MEN2A , MEN2B , FMTC , or HSCR associated ret mutants . ^^^ Recently , it has been shown that glial cell line derived neurotrophic factor ( GDNF ) , by binding to the accessory molecule GDNFR alpha , acts as a functional ligand of Ret and stimulates its tyrosine kinase and biological activity . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Levels of mRNA for neurotrophins ( brain derived neurotrophic factor , BDNF ; neurotrophin 3 , NT 3 ; neurotrophin 4 , NT 4 ) and their receptors ( trkA , trkB , trkC ) and for glial cell line derived neurotrophic factor ( GDNF ) and its receptors ( ret , GDNFR alpha ) were measured in rat thyroid tissue by ribonuclease protection assays . ^^^ An opposite result has been found for the neurotrophic factor GDNF : thyroid tissue showed a high level of transcripts for the GDNF receptor subunits ( GDNFR alpha and Ret ) , while GDNF mRNA was undetectable . ^^^ The in situ hybridization analysis of GDNFR alpha and ret mRNA revealed an interesting difference in the cell distribution of these transcripts : ret mRNA is selectively expressed in a subpopulation of cells scattered in the follicular epithelium and in the interfollicular spaces , while GDNFR alpha expression is more homogeneous and widespread , including the more abundant cell type of the thyroid gland : the follicular cell . ^^^ Double labeling in situ hybridization / immunocytochemistry experiments , with a specific marker ( calcitonin ) , showed that parafollicular cells express ret but not GDNFR alpha . ^^^ This differential distribution of the GDNF receptor components ( GDNFR alpha and ret ) may reflect a peculiar biological role in intercellular communication in the thyroid gland . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Here we describe expression studies of ret , GDNF , and a co receptor for GDNF ( GDNFR alpha ) in the developing mouse metanephros , lung , and submandibular salivary gland . ^^^ At the initiation of metanephric development , late on embryonic day 10 ( E 10 ) , ret and GDNFR alpha were detected in the Wolffian duct ( including the presumptive ureteric bud ) whilst the presumptive metanephric , mesenchyme expressed GDNFR alpha and GDNF . ^^^ At this time ret was expressed throughout the epithelium ; GDNF was detected throughout the mesenchyme , and GDNFR alpha was present in the proximal epithelium and mesenchyme only . ^^^ Ret and GDNF were not detected in the epithelium or mesenchyme of the developing salivary gland , however , GDNFR alpha was expressed in the mesenchyme at E13 . 5 and E16 . 5 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
A marked enhancement of the gene expression for GDNF receptor alpha ( GDNFR alpha ) , which is a component of GDNF receptor , was observed in DRG neurons after sciatic nerve transection , but the percentage of c ret mRNA expressing neurons was not changed . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
By using RT PCR , we studied the expression of the glial cell line derived neurotrophic factor ( GDNF ) , its cell surface receptor alpha ( GDNFR alpha ) , and the receptor tyrosine kinase c ret , known to play a major role in renal organogenesis . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The steady state mRNA levels of glial cell line derived neurotrophic factor ( GDNF ) , GDNFR alpha and RET were examined in various human peripheral neuropathies to determine the relationship with myelinated fiber pathology , and T cell and macrophage invasions in the diseased nerves . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
OBJECTIVE : To investigate the expression of glial cell derived neurotrophic factor ( GDNF ) and its receptor GDNFR alpha ( GFRalpha 1 ) and GDNFR beta ( Ret ) genes and the effects of muscarinic receptor antagonists , NMDA receptor antagonist , inhibitor of nitric oxide synthase on the expression of these genes in the spinal cord , brainstem and frontal cortex during morphine withdrawal , and to observe the effects of GDNF antisense oligoneucleotide ( i . c . v ) on the morphine withdrawal symptoms in rats . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Expression of GDNF receptor ( RET and GDNFR alpha ) mRNAs in the spinal cord of patients with amyotrophic lateral sclerosis . ^^^ The mRNA levels of RET and GDNFR alpha were studied in the spinal cord of patients with amyotrophic lateral sclerosis ( ALS ) by reverse transcription followed by polymerase chain reaction ( RT PCR ) and in situ hybridization ( ISH ) . ^^^ Semiquantitative RT PCR analysis revealed that RET mRNA levels in the ALS spinal cord anterior horn were reduced to one fifth of controls in proportion to motor neuron loss , whereas GDNFR alpha mRNA was unchanged . ^^^ ISH analysis showed that RET mRNA was expressed in the anterior horn motor neurons of the spinal cord , but GDNFR alpha mRNA was expressed widely in the spinal cord neurons and glial cells . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The RET gene product represents the signal transducing molecule of a surface receptor complex for the glial cell line derived neurotrophic factor ( GDNF ) , which includes GDNFR alpha as a ligand binding component . ^^^ Finally , while transcripts specific for GDNF and GDNFR alpha were never found in leukaemic blasts , stromal cells of the haemopoietic microenvironment expressed , in the absence of RET , significant amounts of both GDNF and GDNFR alpha . ^^^ Our results suggest a role for RET in the functional regulation of AMLs through interactions with GDNF and GDNFR alpha producing stromal cells . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
RET is activated by a ligand complex comprising glial cell line derived neurotrophic factor ( GDNF ) and GDNF receptor alpha ( GDNFR alpha ) . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The mRNA expression levels of GDNF , GDNFR alpha and RET were examined in the muscles of amyotrophic lateral screlosis ( ALS ) and 10 linked spinal and bulbar muscular atrophy ( SBMA ) . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
OBJECTIVE : We examine the effects of the administration of therapeutically relevant concentrations of lithium on the expression of brain derived neurotrophic factor ( BDNF ) and its receptor , Trk B , as well as glia derived neurotrophic factor ( GDNF ) and its receptors , RET and GDNFR alpha , in the rat brain . ^^^ In addition , acute or chronic lithium treatments did not change the levels of Trk B , RET , or GDNFR alpha immunoreactivity . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Expressions of GDNF , GDNFR alpha and Ret proteins in the brain of rats with seizures induced by pilocarpine ] . ^^^ The expression patterns of GNDF , GDNFR alpha and Ret were observed dynamically with immunohisto chemical technique , and the extent of neuron damage was assessed by HE stain . ^^^ RESULTS : ( 1 ) GDNF positive cells began to appear 2 hours after SE and reached the peak in 1 and 3 days , then decreased to the normal level ; ( 2 ) GDNFR alpha positive cells in the cortex increased rapidly to the peak 2 hours after SE , and only few such cells were found in hippocampus ; ( 3 ) Ret positive cells were found both in the cortex and hippocampus , with the maximum of expressions 6 8 hours after SE ; ( 4 ) There were some connection between GDNF expression levels and extent of neurons damage . ^^^ CONCLUSION : There exist time dependent upregulations of GDNF , GDNFR alpha and Ret protein in the cortex and hippocampus of rats after SE . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Mutation analysis of glial cell line derived neurotrophic factor ( GDNF ) , a ligand for the RET / GDNF receptor alpha complex , in sporadic phaeochromocytomas . ^^^ Recent data have suggested that glial cell line derived neurotrophic factor ( GDNF ) is a ligand for RET and acts via a heterotetrameric receptor complex that includes GDNF receptor alpha , which provides ligand binding capabilities , and RET , which provides the signaling component . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
By in situ hybridization , we now show that IHCs of the neonatal and mature rat cochlea synthesize GDNF and that GDNF receptor alpha , but not c Ret , is expressed in the rat spiral ganglion . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
In the present work , we first examined c ret and GDNF receptor alpha 1 ( GFR alpha 1 ) expression using an RNAse protection assay , and found that both receptors are expressed in the adult rat striatum . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
It has been shown recently that GDNF signals through the receptor tyrosine kinase Ret and the GDNF receptor alpha ( GFR alpha ) . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The receptor for glial cell line derived neurotrophic factor ( GDNF ) consists of GFRalpha 1 and Ret . ^^^ Both GFRalpha 1 and GFRalpha 2 mediate neurturin induced Ret phosphorylation . ^^^ GDNF can also bind to either GFRalpha 1 or GFRalpha 2 , and activate Ret in the presence of either binding receptor . ^^^ Cross linking and Ret activation data also suggest that while there is cross talk , GFRalpha 1 is the primary receptor for GDNF and GFRalpha 2 exhibits a preference for neurturin . ^^^ Analysis of the tissue distribution of GFRalpha 1 , GFRalpha 2 , GFRalpha 3 , and Ret by Northern blot reveals overlapping but distinct patterns of expression . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Despite the similarity of GFRalpha 3 to GFRalpha 1 and GFRalpha 2 , it is unable to activate Ret in conjunction with GDNF , suggesting that there are likely additional undiscovered ligands and / or Ret like receptors to be identified . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GDNF and neurturin signal through a multicomponent receptor complex containing a signaling component ( the Ret receptor tyrosine kinase ) and either of two glycosyl phosphatidylinositol linked binding components ( GDNF family receptor alpha components 1 and 2 , GFRalpha 1 or GFRalpha 2 ) , whereas the receptor for persephin is unknown . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Thus , all three GFR alpha receptors mediate GDNF binding to c Ret with efficiencies GFR alpha 1 > GFR alpha 2 > GFR alpha 3 . c Ret showed high levels of constitutive tyrosine autophosphorylation upon overexpression in COS cells , which was inhibited in a dose dependent manner by coexpression with any of the GFR alpha receptors , suggesting that GFR alpha s may also provide a gain control mechanism to increase the signal to noise ratio of the response to ligand . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Both GDNF and neurturin signal via a two component receptor complex that consists of a ligand binding GDNF family receptor ( GFRalpha 1 or GFRalpha 2 ) and the receptor protein tyrosine kinase Ret . ^^^ In addition , we present evidence in vitro that GFRalpha 1 mediates Ret activation by GDNF in trans . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
We show that mice who are deficient in the glycosyl phosphatidyl inositol ( GPI ) linked protein GFRalpha 1 ( GDNFRalpha ) display deficits in the kidneys , the enteric nervous system , and spinal motor and sensory neurons that are strikingly similar to those of the GDNF and Ret deficient mice . ^^^ Taken together with the available genetic and biochemical data , these findings support the idea that GFRalpha 1 and the transmembrane tyrosine kinase Ret are both necessary receptor components for GDNF in the developing kidney and nervous system , and that GDNF and neurturin can mediate some of their activities through a second receptor . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The receptor for these factors is a multicomponent complex that includes the RET ( rearranged during transfection ) tyrosine kinase receptor and one of two glycosyl phosphatidylinositol ( GPI ) linked ligand binding components called GDNF family receptor alphas ( GFRalpha 1 and GFRalpha 2 ) . ^^^ We have used in situ hybridization to study the mRNA expression of NTN , GDNF , RET , GFRalpha 1 , and GFRalpha 2 in the central nervous system ( CNS ) of adult mice . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GDNF and neurturin signal through multicomponent receptors that consist of the Ret receptor tyrosine kinase and one of two structurally related glycosyl phosphatidylinositol ( GPI ) linked ligand binding subunits : GFR alpha 1 is the preferred ligand binding subunit for GDNF , and GFR alpha 2 is the preferred ligand binding subunit for neurturin . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Fibroblasts transfected with Ret and one of the coreceptors GFRalpha 1 or GFRalpha 2 do not respond to persephin , suggesting that persephin utilizes additional , or different , receptor components than GDNF and NTN . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Here we show that these neurons express the receptor components for glial derived neurotrophic factor ( GDNF ) signaling ( RET , GFRalpha 1 , and GFRalpha 2 ) . ^^^ In lumbar dorsal root ganglia , virtually all IB 4 labeled cells express RET mRNA , and the majority of these cells ( 79 % ) also express GFRalpha 1 , GFRalpha 2 , or GFRalpha 1 plus GFRalpha 2 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GDNF uses a multisubunit receptor system in which GFRalpha 1 and Ret function as the ligand binding and signalling components , respectively . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Neurturin ( NTN ) is a neuronal survival factor that activates the Ret tyrosine kinase in the presence of a GPI linked coreceptor ( either GFR alpha 1 or GFR alpha 2 ) . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Glial cell line derived neurotrophic factor ( GDNF ) and a related protein , neurturin ( NTN ) , require a GPI linked coreceptor , either GFR alpha 1 or GFR alpha 2 , for signaling via the transmembrane Ret tyrosine kinase . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
To test the involvement of c Src in Ret mediated signaling , we measured the levels of c Src activity in NIH3T3 cells coexpressing Ret and the accessory GFR alpha 1 receptor or an epidermal growth factor receptor / Ret chimeric receptor when the cells were stimulated by glial cell line derived neurotrophic factor or epidermal growth factor , respectively . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
There was no detectable expression of another GDNF receptor component , a glycosyl phosphatidylinositol linked receptor ( GFR alpha 1 ) , in pancreatic cancer cell lines , suggesting that the neural invasion of pancreatic cancer cells spreads along a concentration gradient of GDNF produced from peripheral ganglions through direct interaction of GDNF with its receptor , the c ret proto oncogene product . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GFRalpha 1 can be coexpressed with GFRalpha 2 and c Ret mRNAs in the same hippocampal or thalamic neurons , but other neurons contain GFRalpha 1 alone or together with c Ret mRNA . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
METHODS : Cryosections of fetal and newborn stomach , ileum , and colon were hybridized in situ with S 35 labeled cRNA probes to GDNF , Ret , GFRalpha 1 or GFRalpha 2 . ^^^ Ret , GFRalpha 1 and GFRalpha 2 mRNA were expressed in the ganglionic cells of both myenteric and submucosal plexuses throughout the intestine . ^^^ Ret , GFRalpha 1 , and GFRalpha 2 most likely act as GDNF receptors in colon but may have alternative ligands in other enteric segments . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Signaling by GDNF and NTN depends on the tyrosine kinase receptor Ret and on GFRalpha 1 and 2 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
It is well documented that RET / GFRalpha 1 / GDNF delivers a signal critical for the survival of the early neural crest derived precursors that colonize the intestine below the rostral foregut and give rise to the enteric nervous plexuses [ Gershon , 1997 ; Cacalano et al . , 1998 ; Enomoto et al . , 1998 ] . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Glial cell line derived neurotrophic factor ( GDNF ) and neurturin ( NTN ) mediate their actions through a unique multicomponent receptor system composed of Ret receptor tyrosine kinase and glycosyl phosphatidylinositol linked cell surface proteins ( designated GFRalpha 1 and GFRalpha 2 ) . ^^^ In contrast , bone marrow stromal cells appeared to express GDNF , GFRalpha 1 and GFRalpha 2 but not Ret . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Furthermore , OLI neu and OLN 93 cells expressed transcripts encoding the GDNF receptors Ret and GFRalpha 1 . ^^^ Similarly , primary O 2A progenitor cells and enriched mature oligodendrocytes expressed Ret , GFRalpha 1 and GFRalpha 2 mRNAs . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GDNF binds preferentially to GFR alpha 1 , NTN GFR alpha 2 , ART GRF alpha 3 , and PSP GFR alpha 4 as a co receptor to activate Ret . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Upregulation of GFRalpha 1 and c ret in primary sensory neurons and spinal motoneurons of aged rats . ^^^ The established signaling mechanism for the GDNF / GFRalpha 1 complex is through binding to the tyrosine kinase receptor encoded by the c ret proto oncogene , and we also show here that c ret mRNA is upregulated in both motoneurons and primary sensory neurons of aged rats . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
In an attempt to elucidate whether glial cell line derived neurotrophic factor ( GDNF ) receptors are induced after ischemic brain injury , possible expression of immunoreactive GDNF receptor alpha 1 ( GFRalpha 1 ) and c ret ( RET ) was examined at 3 , 8 , or 24 h after permanent middle cerebral artery occlusion ( MCAO ) in rats . ^^^ Immunohistochemical study showed that both GFRalpha 1 and RET staining cells which were not detected in sham control brain , were present in the ipsilateral cortex and caudate at 3 to 8 h after permanent MCAO , and then decreased but remained to some extent at 24 h . ^^^ This rapid induction of GFRalpha 1 and RET , which correlates with the similar induction of GDNF under these conditions , may play a role in the early response to ischemic brain injury . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Following hypoglossal nerve axotomy in neonate rat , Glial cell line Derived Neurotrophic Factor ( GDNF ) receptor alpha 1 ( GFRalpha 1 ) mRNA expression was dramatically suppressed in the injured motoneurons , while a slight increase of c Ret mRNA expression was observed . ^^^ In adult , both GFRalpha 1 and c Ret mRNAs increased substantially after axotomy . ^^^ The present result suggests that the difference of motoneuron fate after axotomy may be partly due to the coordinate or discordant responses of GFRalpha 1 and c Ret expression to nerve injury . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Mutation and deletion analysis of GFR alpha 1 , encoding the co receptor for the GDNF / RET complex , in human brain tumours . ^^^ GDNF preferentially binds to GFRalpha 1 which then interacts with the receptor tyrosine kinase RET . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GDNF , RET and GFRalpha 1 3 mRNA expression in the developing human spinal cord and ganglia . ^^^ Using in situ hybridization , the expression of glial cell line derived neurotrophic factor ( GDNF ) , neurturin ( NTN ) , persephin ( PSP ) , GFRalpha 1 , GFRalpha 2 , GFRalpha 3 and RET mRNA in human fetal spinal cord was studied . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
We show the presence of Ret and GFRalpha 1 , GFRalpha 2 , and GFRalpha 4 in chicken motoneurons using in situ hybridization and reverse transcription PCR techniques . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
In the present study , the expression of GDNF receptors , ret and GFRalpha 1 , was demonstrated in rat primary cultured microglia by reverse transcription polymerase chain reaction and the protein level expression of Ret was also confirmed by Western blotting analyses . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
We postulate that disruption of renal development results because Ret ( MEN2B ) derived from the hyperplastic nervous tissue competes with endogenous renal Ret for gfralpha 1 or other signaling components . ^^^ Constitutive loss of Ret , its co receptor gfralpha 1 , or the ligand glial cell line derived neurotrophic factor results in renal agenesis . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Here we show that upon GDNF binding glycosyl phosphatidylinositol ( GPI ) linked GDNF receptor alpha 1 ( GFRalpha 1 ) activates cytoplasmic Src family tyrosine kinase ( s ) in Ret tyrosine kinase deficient cultured mouse dorsal root ganglion neurons and in two Ret negative cell lines . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Sensitivity to these factors is conferred by a receptor complex consisting of a ligand binding domain ( GFRalpha 1 GFRalpha4 ) and a signal transducing domain RET . ^^^ In normal rats , RET and GFRalpha 1 were expressed in a subpopulation of both small and large diameter afferents projecting through the sciatic nerve [ 60 and 40 % of FluoroGold ( FG ) labeled cells , respectively ] . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The receptors for these factors are complexes that include the Ret tyrosine kinase receptor and a GPI linked , ligand binding component called GDNF family receptor alpha 1 4 ( GFRalpha 1 4 ) . ^^^ We have used in situ hybridization to study the mRNA expression of NRTN , GDNF , Ret , GFRalpha 1 , and GFRalpha 2 during embryonic development and in the adult mouse . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The second , associated with mutations in genes encoding glial cell line derived neurotrophic factor ( GDNF ) , its preferred receptor GFRalpha 1 , or their signaling component , Ret , appears to deprive a GDNF dependent common progenitor of adequate support and / or mitogenic drive . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Using in situ hybridization histochemistry , we characterized the spatiotemporal gene expression patterns of leukemia inhibitory factor ( LIF ) and glial cell line derived neurotrophic factor ( GDNF ) , and their receptor components ( LIFR , GFR alpha 1 , RET ) induced in muscle cells , intramuscular nerves , and motoneurons in the regeneration processes of both muscle cells and nerves following muscle contusion . ^^^ LIFR , GFR alpha 1 , and RET mRNA expressions in motoneurons were upregulated following muscle contusion . ^^^ Muscle contusion also induced more rapid , prominent transactivations of GFR alpha 1 and RET genes in motoneurons than did sciatic nerve axotomy . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Neurturin , RET , GFRalpha 1 and GFRalpha 2 , but not GFRalpha 3 , mRNA are expressed in mice gonads . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The GDNF family ligands ( GFLs : GDNF , neurturin , persephin , and artemin ) signal through RET and a gly cosyl phosphatidylinositol ( GPI ) anchored coreceptor ( GFRalpha 1 alpha4 ) that binds ligand with high affinity and provides specificity . ^^^ Here , we report that GPI anchored GFRalpha 1 recruits RET to lipid rafts after GDNF stimulation and results in RET / Src association . ^^^ Disruption of RET localization using either transmembrane anchored or soluble GFRalpha 1 results in RET phosphorylation , but GDNF induced intracellular signaling events are markedly attenuated as are neuronal differentiation and survival responses . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
First of all , RT PCR analysis , Western blot and immunohistochemistry of the whole anterior pituitary showed that GDNF , GFRalpha 1 and RET are expressed in this gland . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
METHODS : To address this hypothesis , we first investigated ( by RT PCR ) the expression of GDNF mRNA and the mRNAs of the GDNF receptors Ret and GFRalpha 1 in ( 1 ) adult human renal cortex and medulla and ( 2 ) in HMC in culture . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Functional mapping of receptor specificity domains of glial cell line derived neurotrophic factor ( GDNF ) family ligands and production of GFRalpha 1 RET specific agonists . ^^^ The GFLs signal through a multicomponent receptor complex comprised of a high affinity binding component ( GDNF family receptor alpha component ( GFRalpha 1 GFRalpha4 ) ) and the receptor tyrosine kinase RET . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
In this paper , we show that mice with a null mutation of the GFRalpha 1 gene manifest epithelial mesenchymal interaction deficits in kidney and severe disturbances of intestinal tract development similar to those seen with glial cell line derived neurotrophic factor or Ret null mutations . ^^^ Taken together with previous data on glial cell line derived neurotrophic factor and Ret , our results strongly suggest that GFRalpha 1 is the essential GFRalpha receptor for signaling in the glial cell line derived neurotrophic factor Ret pathway in the kidney and enteric nervous system development , and that GFRalpha 2 or GFRalpha 3 can not substitute for the absence of GFRalpha 1 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Here we show that Ret , GFRalpha 1 ( the GDNF receptor ) , and GFRalpha 2 ( the NTN receptor ) are expressed by testicular germ cells , while GDNF and NTN are expressed by Sertoli cells . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
We used RT PCR to examine the expression of GDNF , neurturin , artemin , persephin and their receptors GFRalpha 1 , GFRalpha 2 , GFRalpha 3 and c ret in whole rat cochlea as well as in functionally different subfractions ( modiolus and sensorineural epithelium / lateral wall ) and compared the levels of neurotrophin and receptor mRNAs in the cochlea to those in substantia nigra brain region . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
However , c ret , which is thought to mediate a signal evoked by binding of GDNF to GFRalpha 1 , was not expressed in the capillaries of the brain cortex in 3 mo old rats . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
There were no obvious non neuronal defects in hearts of Ret , GFRalpha 1 , or GFRalpha 2 deficient mice , suggesting that these receptors are not essential for gross cardiac development . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Expression analysis of RET and the GDNF / GFRalpha 1 and NTN / GFRalpha 2 ligand complexes in pheochromocytomas and paragangliomas . ^^^ Glial cell line derived neurotrophic factor ( GDNF ) and neurturin ( NTN ) have been shown to function as independent ligands to RET , binding in a complex with the membrane bound receptors GFRalpha 1 and GFRalpha 2 respectively . ^^^ Here we have investigated the mRNA expression of RET and its ligand complexes , GDNF / GFRalpha 1 and NTN / GFRalpha 2 , in a panel of pheochromocytomas and paragangliomas using mRNA in situ hybridization . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
After all types of injury , the mRNAs for GDNF receptors ( GFRalpha 1 and c RET ) and the LIF receptor LIFR were distinctly ( up to 300 % ) up regulated in motoneurons . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
To activate RET they form a tripartite complex with RET and a member of a family of four extracellular , GPI linked alpha receptors ( GFR alpha 1 4 ) . ^^^ Targeted mutagenesis in transgenic mice has shown that Ret , GFR alpha 1 and GDNF are required for multiple developmental events including development of the enteric nervous system ( ENS ) affected in Hirschsprung ' s disease . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Expression of RET and its ligand complexes , GDNF / GFRalpha 1 and NTN / GFRalpha 2 , in medullary thyroid carcinomas . ^^^ Glial cell line derived neurotropic factor ( GDNF ) and its membrane bound GDNF family receptor alpha ( GFRalpha 1 ) , as well as neurturin ( NTN ) and its membrane bound receptor GFRalpha 2 form a complex with the RET product , a receptor tyrosine kinase , resulting in downstream signaling to the nucleus . ^^^ METHODS : The mRNA expression of RET , GDNF , GFRalpha 1 , NTN and GFRalpha 2 was investigated by mRNA in situ hybridization , and confirmed by reverse transcription PCR analysis . ^^^ All MTCs showed expression of RET , 13 expressed GDNF , 12 expressed GFRalpha 1 and 9 expressed NTN and GFRalpha 2 . ^^^ In 7 of the tumors RET , GDNF and GFRalpha 1 were expressed at high levels , and in five of these seven tumors NTN and GFRalpha 2 genes were also expressed at high levels . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
They exert their biological effects by activating the RET tyrosine kinase in the presence of a glycosyl phosphatidylinositol linked co receptor , either GFRalpha 1 or GFRalpha 2 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
In wild type control embryos , all brachial and lumbar MNs appear to express the GDNF receptors c ret and GFRalpha 1 and the MN markers ChAT , islet 1 , and islet 2 , whereas only a small subset express GFRalpha 2 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
In newborn GFRalpha 1 or Ret deficient mice , where many submandibular ganglion neurons were still present , the otic and sphenopalatine ganglia were completely missing . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The influence of both acute and chronic electroconvulsive seizure ( ECS ) or antidepressant drug treatments on expression of mRNAs encoding glial cell line derived neurotrophic factor ( GDNF ) and its receptors , GFRalpha 1 , GFRalpha 2 , and c Ret proto oncogene ( RET ) in the rat hippocampus was examined by in situ hybridization . ^^^ Chronic ( 14 days ) administration of different classes of antidepressant drugs , including tranylcypromine , desipramine , or fluoxetine , did not significantly affect the GDNF , GFRalpha 1 , GFRalpha 2 , or RET mRNA levels in CA 1 , CA 3 , and dentate gyrus areas of hippocampus . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
However , the expression pattern of GDNF and its receptor complex the GPI linked ligand binding protein , GFRalpha 1 , and the Ret tyrosine kinase signaling protein indicates that it could operate at early steps in kidney development as well . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Although all GDNF family ligands signal via activated Ret , GDNF can signal also via GFRalpha 1 in the absence of Ret . ^^^ GDNF binding to GFRalpha 1 also recruits Ret to the lipid rafts and triggers association with Src , which is required for effective downstream signalling , leading to differentiation and neuronal survival . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Migrating neural cells and neurites from the esophagus and midgut accumulated around the GDNF impregnated beads , but neural cells in other tissues showed little or no chemotactic response to GDNF , although all showed GDNF receptor ( Ret and GFRalpha 1 ) immunoreactivity . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
They exert their biological effects by activating the RET tyrosine kinase in the presence of a GPI linked coreceptor , either GFR alpha 1 ( considered to be the favored coreceptor for GDNF ) or GFR alpha 2 ( the preferred NTN coreceptor ) . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Over representation of a germline variant in the gene encoding RET co receptor GFRalpha 1 but not GFRalpha 2 or GFRalpha 3 in cases with sporadic medullary thyroid carcinoma . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Expression of GFR alpha 1 , GFR alpha 2 , and c Ret mRNAs in rat adrenal gland . ^^^ Glial cell line derived neurotrophic factor ( GDNF ) , an important factor for developing and lesioned pre and postganglionic sympathetic neurons , and its congeners signal through a receptor complex consisting of the tyrosine kinase c Ret and a lipid anchored alpha receptor ( GFR alpha 1 4 ) . ^^^ Coexpression of c Ret and GFR alpha 1 mRNA ' s is restricted to a scarce subpopulation of medullary sympathetic neurons . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
We have also investigated the role of Ca ( 2+ ) in ligand binding by RET and found that Ca ( 2+ ) ions are required for RET binding to GDNF but not for GDNF binding to the GFRalpha 1 co receptor . ^^^ In agreement with these results , RET , but not GFRalpha 1 , was found to bind Ca ( 2+ ) directly . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Expression of RET , GFRalpha 1 , and neuronal nitric oxide synthase ( nNOS ) was assessed by Western blot and immunocytochemistry . ^^^ RESULTS : Our results show that CNS NSC express both the receptors ( RET and GFRalpha 1 ) for the enteric neurotrophin , GDNF ; GDNF , in turn , induces expansion of the RET expressing CNS NSC population . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Messenger RNA was found encoding RET , GFR alpha 1 , BDNF , trkB , and trkC in the adult human spinal cord and BDNF , NT 3 , p 75 , trkB , and trkC in the fetal human spinal cord . ^^^ The percentage of adult human DRG cells expressing p 75 , trkA , trkB , or trkC was 57 , 46 , 29 , and 24 % , respectively , and that of DRG cells expressing RET , GFR alpha 1 , GFR alpha 2 , or GFR alpha 3 was 79 , 20 , 51 , and 32 % , respectively . ^^^ GFR alpha 2 was expressed selectively in small , GFR alpha 3 principally in small and GFR alpha 1 and RET in both large and small adult human DRG neurons . p 75 and trkB were expressed by a wide range of DRG neurons while trkA was expressed in most small diameter and trkC primarily in large DRG neurons . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GFLs bind to specific glycosyl phosphatidylinositol ( GPI ) anchored co receptors ( GFRalpha 1 alpha4 ) , but signal through a common c Ret receptor . ^^^ Both GPI anchored and soluble GFRalpha 1 recruit c Ret to lipid rafts following GDNF stimulation , where c Ret interacts with different proteins than outside the rafts . ^^^ Soluble GFRalpha 1 mobilizes c Ret to rafts by a different mechanism compared with GPI anchored GFRalpha1 . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Both c Ret and GFRalpha 1 mRNA levels were markedly increased in the ipsilateral cortex outside the ischemic lesion at 6 24 h after the 2 h insult , whereas GFRalpha 2 expression was decreased in cortical areas both within and outside the lesion . ^^^ Similar increases of c Ret and GFRalpha 1 mRNA levels were detected in the striatum , and to a lesser extent , in the cortex following 30 min of MCAO . ^^^ The 2 h insult also gave rise to transient increases of c Ret and GFRalpha 1 mRNA in hippocampal subregions . ^^^ Thirty minutes and 2 h of MCAO lead to elevated c Ret , and GFRalpha 1 or GFRalpha 2 mRNA expression , respectively , in the ipsilateral ventroposterolateral thalamic nucleus . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Since the down regulation of GDNF in the eye is accompanied by down regulation of GFRalpha 1 and Ret , but not of GFRalpha 2 , in innervating ciliary ganglion neurons , the results also suggest that target derived GDNF regulates the expression of its high affinity coreceptors . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
In addition , it has been demonstrated that GDNF can signal through GFRalpha 1 in the absence of c Ret . ^^^ To establish an assay system for these studies , several neural cell lines were screened for the presence of GDNF and NTN receptor subunits by RT PCR and immunoblot analysis . c Ret expression was detectable only in Neuro2A cells , which did not express GFRalpha 1 or GFRalpha 2 . ^^^ Together these findings provide evidence that , in contrast to GFRalpha 1 , GFRalpha 2 fails to signal in the absence of c Ret . ^^^ In addition , these observations reveal that c Ret independent signaling of GFRalpha 1 is ligand specific and occurs only with GDNF . . ^^^ Evidence for a ligand specific signaling through GFRalpha 1 , but not GFRalpha 2 , in the absence of Ret . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
RET ( Men2B ) transgene produces sympathoadrenal tumors but does not prevent intestinal aganglionosis in gdnf / or gfr alpha 1 ( / ) mice . ^^^ In vitro studies have shown that the kinase and mitogenic properties of RET ( Men2B ) are enhanced by GDNF / GFR alpha 1 stimulation . ^^^ A relevant clinical question is whether ablation of either GDNF or GFR alpha 1 could alter penetrance or severity of the MEN2B syndrome . ^^^ We report that ganglioneuromatous tumors caused by a RET ( Men2B ) transgene in mice are not affected grossly or microscopically by the absence of gdnf or gfr alpha 1 . ^^^ We find that expression of the RET ( Men2B ) transgene in enteric neural progenitors , after they colonize the gut , does not prevent intestinal aganglionosis associated with gdnf or gfr alpha 1 deficiency . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Activation of RET requires the secreted neurotrophin GDNF ( glial cell line derived neurotrophic factor ) and its high affinity receptor , a glycosyl phosphatidylinositol linked cell surface protein GFRalpha 1 . ^^^ In the developing kidney , RET , GDNF , and GFRalpha 1 are all required for directed outgrowth and branching morphogenesis of the ureteric bud epithelium . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
In this paper we demonstrate GDNF , GFRalpha 1 , and RET mRNA and protein expression in the human anterior pituitary gland . ^^^ All of the remaining pituitary tumors screened were negative for RET , GDNF , and GFRalpha 1 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
In order to explore the role of RET , GFR alpha 1 and GDNF genes in the variation of phenotypes observed in MEN2A families , we analysed germline mutations of these genes in 4 unrelated Spanish MEN2A families ( 23 cases studied ) . ^^^ Genetic analysis of RET , GFR alpha 1 and GDNF genes in Spanish families with multiple endocrine neoplasia type 2A . ^^^ We found 2 novel variants corresponding to a single change in position + 47 ( intron 12 ) of RET and position +22 ( intron 7 ) of GFR alpha 1 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
This study was conducted to determine whether neurotrophic factor receptors ( tyrosine kinase receptors trkA , trkB , and trkC ; low affinity neurotrophin [ NT ] receptor p 75 [ p 75 ( NTR ) ] ; glial cell line derived neurotrophic factor receptor alpha 1 [ GFR alpha 1 ] and GFR alpha 2 ; and Ret ) are involved in the formation of ERMs after PDR . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
We also found that the receptor for GDNF , GFRalpha 1 , and its signaling moiety c Ret were upregulated , starting immediately after ischemia . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Here we report the expression of RET isoforms and its signalling complex , GDNF and GFRalpha 1 , in foetal and adult human kidneys . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GDNF and the GDNF receptors , c Ret , GFR alpha 1 and 2 mRNA is expressed in the developing chicken retina . ^^^ GDNF labelling was mainly found in embryonic day 4 5 retina but weak labelling could also be found over scattered retinal cells at later stages . c ret labelling was found over ganglion cells , amacrine and horizontal cells ; the preferred GDNF receptor ( GFR alpha 1 ) over amacrine and horizontal cells ; and the less preferred GDNF receptor ( GFR alpha 2 ) over ganglion cells , amacrine cells and photoreceptors . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Regulation of c Ret , GFRalpha 1 , and GFRalpha 2 in the substantia nigra pars compacta in a rat model of Parkinson ' s disease . ^^^ We evaluated the changes in the expression of c Ret , GFRalpha 1 , and GFRalpha 2 in the substantia nigra pars compacta in a rat model of Parkinson ' s disease by in situ hybridization . ^^^ Intrastriatal injection of 6 hydroxydopamine ( 6 OHDA ) transiently increased c Ret and GFRalpha 1 mRNA levels in the substantia nigra pars compacta at 1 day postlesion . ^^^ At later time points , 3 and 6 days , the expression of c Ret and GFRalpha 1 was downregulated . ^^^ Triple labeling studies , using in situ hybridization for the GDNF family receptors and immunohistochemistry for neuronal or glial cell markers , showed that changes in the expression of c Ret , GFRalpha 1 , and GFRalpha 2 in the substantia nigra pars compacta were localized to neurons . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
A relative deficit of GFRalpha 1 in developing axons allows exogenous GFRalpha 1 to capture GDNF and present it for recognition by axonal c Ret receptors . ^^^ Exogenous GFRalpha 1 potentiates neurite outgrowth and acts as a long range directional cue by creating positional information for c Ret expressing axons in the presence of a uniform concentration of GDNF . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Here we show that GDNF requires glycosaminoglycans as well as the already known components of its receptor complex , c Ret and GFRalpha 1 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GDNF and NRTN bind to the tyrosine kinase receptor Ret and the receptors GFRalpha 1 and GFRalpha 2 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Recently , we described two possible low penetrance susceptibility alleles in the gene encoding RET coreceptor GFRalpha 1 , 193C > G and 537T > C , in a German series of sMTC . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Differential expression of the GDNF family receptors RET and GFRalpha 1 , 2 , and 4 in subsets of motoneurons : a relationship between motoneuron birthdate and receptor expression . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Similar phenotypes arise from targeted disruption of the genes encoding either GDNF , or its receptors , GFRalpha 1 and c Ret . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
To clarify the role of Ret signaling components in enteric nervous system ( ENS ) development , we evaluated ENS anatomy and intestinal contractility in mice heterozygous for Ret , GFRalpha 1 and Ret ligands . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Some trace residues had been proved to be important in ligand receptor binding , especially in rat GFRalpha 1 , where alanine scanning mutagenesis confirmed that sites N ( 152 ) N ( 153 ) , R ( 259 ) , S ( 316 ) N ( 317 ) S ( 318 ) and Q ( 247 ) D ( 248 ) S ( 249 ) were critical for GFRalpha 1 binding to GDNF or Ret and thus affected the formation of GDNF GFRalpha 1 Ret complex . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Cerebral ischemia induces gene expression of GDNF , GDNF receptor alpha 1 ( GFRalpha 1 ) and c Ret , suggesting that a GDNF signaling cascade mechanism may be involved in endogenous neuroprotection during ischemia . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The neurotrophic activities of GDNF are mediated by binding to GFRalpha 1 and further interaction of the GDNF GFRalpha 1 complex with a coreceptor tyrosine kinase encoded by the c Ret protooncogene . ^^^ Internalization of glial cell derived neurotrophic factor receptor GFR alpha 1 in the absence of the ret tyrosine kinase coreceptor . 1 . ^^^ There is also evidence for the existence of cell signaling by GDNF and GFRalpha 1 in the absence of Ret . 2 . ^^^ To further delineate the Ret dependent and independent functions of GDNF , cellular internalization of GDNF and GFRalpha 1 was examined in cells lines and primary neurons . 3 . ^^^ Relative to other GPI anchored receptors , efficient endocytosis ( approximately 30 40 % of total surface bound ligand internalized after 2 min ) of GNDF and GFRalpha 1 was observed in neuroblastoma and transfected fibroblast cell lines that lack Ret . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
It binds to and activates a receptor complex consisting of GFR alpha 1 and Ret receptor tyrosine kinase . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
In the present study we profile the expression of GDNF and its receptor complex ( Ret and GFRalpha 1 ) in cells isolated from the human optic nerve head ( ONH ) . ^^^ Total RNA was isolated and subjected to reverse transcriptase polymerase chain reaction ( RT PCR ) to examine mRNA expression of GDNF , Ret , and GFRalpha 1 . ^^^ RESULTS : Lamina cribrosa cells , ONH astrocytes , and LC tissues expressed messenger RNA for GDNF , Ret and GFRalpha 1 . ^^^ Lamina cribrosa cells and ONH astrocytes also expressed protein for GDNF , Ret , and GFRalpha 1 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Whereas it is well established that GDNF affects dopaminergic cell survival through a receptor complex composed of the tyrosine kinase , Ret , and the glycosylphosphatidylinositol ( GPI ) anchored protein , GFRalpha 1 , c Ret is basically undetectable in cortical neurons . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Association of NCAM with GFRalpha 1 , a GPI anchored receptor for GDNF , downregulates NCAM mediated cell adhesion and promotes high affinity binding of GDNF to p 140 ( NCAM ) , resulting in rapid activation of cytoplasmic protein tyrosine kinases Fyn and FAK in cells lacking RET , a known GDNF signaling receptor . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Effect of 6 hydroxydopamine on striatal GDNF and nigral GFRalpha 1 and RET mRNAs in the adult rat . ^^^ We therefore investigated whether changes in striatal GDNF protein and nigral mRNA levels of its co receptors GFRalpha 1 and RET occur in response to lesions of dopamine ( DA ) neurons and examined the temporal profile of these changes as they relate to the loss of dopaminergic markers . ^^^ In situ hybridization was used to determine alterations in the mRNAs of RET and GFRalpha 1 in the SN and VTA . ^^^ Dramatic decreases in RET and GFRalpha 1 were observed in both SN and VTA that were generally correlated with the loss of TH protein and striatal DA content , strongly suggesting that these receptors are located on DA neurons and that the protective effect of GDNF reflects a direct action of the trophic factor on these neurons . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Glial cell line derived neurotrophic factor ( GDNF ) , neurturin ( NTN ) and their receptors ( GFRalpha 1 , GFRalpha 2 and Ret ) play an important role in the survival of neurons in the central and peripheral nervous system . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
In addition , Ret and the GFL co receptors GFRalpha 1 and GFRalpha 2 are expressed in developing cholinergic neurons in cultures of embryonic basal forebrain . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GFLs signal through a common receptor tyrosine kinase ( Ret ) and one of the four ligand binding co receptors ( GFRalpha 1 to 4 ) . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
We investigated the immunohistochemical expression of GDNF , NTN , and their receptors ( GFRalpha 1 , 2 , and 3 , and Ret ) in normal human kidney and in 42 nephroblastomas , 20 of which were associated with nephrogenic rests ( group A ) and 22 were not ( group B ) . ^^^ The pathway of activation seems to follow an autocrine / paracrine mechanism , as neurotrophic factors , GFRalpha 1 2 3 receptors and Ret are coexpressed . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The structure of GFRalpha 1 domain 3 reveals new insights into GDNF binding and RET activation . ^^^ Glial cell line derived neurotrophic factor ( GDNF ) binds to the GDNF family co receptor alpha 1 ( GFRalpha 1 ) and activates RET receptor tyrosine kinase . ^^^ Arg 217 may thus be involved in the allosteric properties of GFRalpha 1 or in binding RET . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GDNF , Ret , GFRalpha 1 and 2 in the adult rat retino tectal system after optic nerve transection . ^^^ In the present study , we have studied the expression of glial cell line derived neurotrophic factor ( GDNF ) and its receptors Ret , GFRalpha 1 , and GFRalpha 2 in the retino tectal system before and after optic nerve transection . ^^^ Using retrograde neuronal tracing in combination with in situ hybridization , we found that Ret and GFRalpha 1 are expressed by 13 14 % of the retinal ganglion cells ( RGCs ) . ^^^ Optic nerve transection resulted in reduced Ret mRNA levels in retina , while the levels of GDNF , GFRalpha 1 , and 2 mRNA increased . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
These and other important dopaminergic genes found expressed in these cultures by RT PCR included Nurr 1 , vesicular monoamine transporter 2 ( VMAT 2 ) , TH , dopamine transporter ( DAT ) , and glial cell line derived neurotrophic factor ( GDNF ) receptors c Ret and GFRalpha 1 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The glial cell line derived neurotrophic factor ( GDNF ) family coreceptor alpha 1 ( GFRalpha 1 ) is a critical component of the RET receptor kinase signal transducing complex . ^^^ These results indicate that specific inclusion of the GFRalpha 1 exon 5 in neuronal tissues or during kidney development may alter the binding properties of GDNF to GFRalpha 1 , and thus could constitute an additional regulatory mechanism of the RET signaling pathway . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Our results demonstrate the presence of GDNF receptors RET and GFR alpha 1 in the two cellular compartments , cell bodies and distal axons . ^^^ Retrograde signaling was associated with retrograde transport of radiolabeled GDNF and GFR alpha 1 , as well as activation of RET and AKT , but not of ERK1 / 2 , in cell bodies . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GFRalpha 1 expression in cells lacking RET is dispensable for organogenesis and nerve regeneration . ^^^ To address the physiological significance of these roles , we generated mice specifically lacking RET independent GFRalpha 1 . ^^^ Thus RET independent GFRalpha 1 is dispensable for organogenesis and nerve regeneration in vivo , indicating that trans signaling and GFRalpha dependent NCAM signaling play a minor role physiologically . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
In conjunction with antibody labeling and in situ hybridization , we demonstrate that : ( 1 ) lung ganglia arise from vagal NCC that migrate from the foregut into the lung buds ; ( 2 ) like ENS precursors , these NCC express the transcription factor Sox 10 , and the receptors EDNRB and RET ; ( 3 ) the co receptor for RET , GFRalpha 1 , is expressed in the lung mesenchyme and in ganglia ; ( 4 ) ganglia persist within the lung throughout development and contain cells immunopositive for the pan neuronal markers ANNA 1 and PGP9 . 5 , the inhibitory neurotransmitter NO , as shown by NADPH diaphorase staining , and the glial marker GFAP . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Neuronal expression of GFRalpha 1 , GFRalpha 2 , and ret was confirmed by immunocytochemistry . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
In cell free binding studies , GFRalpha 1 Ig displayed strong preferential binding to GDNF , though in the presence of soluble RET , weak binding to ART could also be detected . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
These effects required GFRalpha 1 but neither RET nor NCAM , the two transmembrane signaling receptors known for GDNF . ^^^ Mutant mice lacking GDNF or GFRalpha 1 , but neither RET nor NCAM , showed reduced numbers of GABAergic cells in the cerebral cortex and hippocampus . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
We found that although all midbrain DA cells express both receptor components of GDNF ( GFRalpha 1 and Ret ) , those in the ventral tegmental area ( VTA ) and rostromedial substantia nigra ( SNrm ) also contain GDNF but not GDNFmRNA . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The ligand activates on the ureteric bud epithelium a receptor complex composed of Ret and GFRalpha 1 . ^^^ Ret and GFRalpha 1 are normally downregulated in the Wolffian duct , but they were persistently expressed in the entire transgenic duct . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Moreover , we found that the biological activity of pro NTN differs from mature NTN , as pro NTN did not form a signaling complex with the tyrosine kinase receptor Ret and GFRalpha 2 or GFRalpha 1 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Transcripts for the ligand specifying receptors for GDNF and neurturin , GFRalpha 1 and GFRalpha 2 , as well as the common signal transducing receptor Ret were all down regulated by RA treatment in a dose dependent manner . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Tissue expression of alternatively spliced GFRalpha 1 , NCAM and RET isoforms and the distinct functional consequence of ligand induced activation of GFRalpha 1 isoforms . ^^^ Glial cell line derived neurotrophic factor ( GDNF ) exerts its effect through a multi component receptor system consisting of GFRalpha 1 , RET and NCAM . ^^^ In this study , isoform specific real time PCR assays were used to quantify the expression levels of GFRalpha 1 , RET and NCAM isoforms in murine embryonic and adult tissues . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
As RET stabilizes the binding of GDNF equally well to the full length and truncated receptors , D 1 seems not to be involved in the interaction between GFRalpha 1 and RET . ^^^ However , when the receptors are overexpressed on the cell surface as GPI anchored proteins , or added to the growth medium at high concentrations as soluble proteins , full length and truncated GFRalpha 1 are indistinguishable in GDNF dependent RET phosphorylation assays . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The isolated cells express Ret , a tyrosine kinase transmembrane receptor that mediates the intracellular response to GDNF via GFR alpha 1 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Ret , GFRalpha 1 , GFRalpha 2 and GFRalpha 3 receptors in the human hippocampus and fascia dentata . ^^^ The immunohistochemical detectability of GFRalpha 1 , GFRalpha 2 , GFRalpha 3 and Ret receptor molecules is shown in the rat up to 72 h post mortem . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GDNF and NTN signaling is mediated by a two component receptor : a signal transducing component , RET , which is shared by both ligands , and a ligand specific binding component , GFR alpha 1 ( higher GDNF affinity ) or GFR alpha 2 ( higher NTN affinity ) . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Glial cell line derived neurotrophic factor ( GDNF ) family receptor alpha 1 ( GFRalpha 1 ) is a receptor component of GDNF that associates with and activates the tyrosine kinase receptor Ret . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
RESULTS : mRNA expression studies of GDNF receptors , GFRalpha 1 and Ret , demonstrated that GDNF receptors were not exclusively expressed by the degenerating photoreceptor cells but mainly by MGC . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The ligands bind RET through GDNF family receptor alpha , termed GFRalpha 1 4 . ^^^ To compare the signaling profiles of GDNF and neurturin , we have identified a cell line , NG 108 15 , which endogenously expresses RET and GFRalpha 1 but not GFRalpha 2 4 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The present study examined the expression of GDNF , GFRalpha 1 , and RET in the incisor periodontal ligament and trigeminal ganglion of young rats by RT PCR and immunocytochemistry . ^^^ Their axonal branches showed GFRalpha 1 and RET immunoreactions but lacked GDNF immunoreactivity . ^^^ In the trigeminal ganglion , about 30 % of the neurons were immunoreactive to GFRalpha 1 and RET . ^^^ These findings indicate that GDNF mediates trophic effects on the survival and target innervation of the periodontal Ruffini endings via GFRalpha 1 and RET . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
We show here that in porcine retina , GDNF receptors GFRalpha 1 and RET are expressed on retinal Mueller glial cells ( RMG ) but not on photoreceptors . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GDNF family ligand receptor components Ret and GFRalpha 1 in the human trigeminal ganglion and sensory nuclei . ^^^ The occurrence of Ret and GFRalpha 1 receptors is shown by immunohistochemistry in the human trigeminal sensory system at pre , postnatal and adult age . ^^^ In adult trigeminal ganglion , about 75 % of Ret and 65 % of GFRalpha 1 labeled neurons are small and medium sized . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
First , we demonstrated continued cortical expression of GDNF receptor components ( GFRalpha 1 , c Ret ) , suggesting that GDNF could have a physiological effect in the immediate post traumatic period . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Regulation of GDNF and its receptor components GFR alpha 1 , alpha 2 and Ret during development and in the mature retino collicular pathway . ^^^ Stable mRNA transcription of GDNF and its receptors GFR alpha 1 , alpha 2 and Ret was found in retina and SC throughout development into adulthood and after ON transection . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Despite the progressive loss of GFRalpha 1 and 2 , phosphorylation of c ret shows no detectable reduction on tyrosine residues or on serine 696 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The gene expression of GDNF , persephin , artemin and neurturin , and their receptors GFRalpha 1 , GFRalpha 2 , GFRalpha 3 and Ret , was determined by semiquantitative reverse transcriptase polymerase chain reaction using GAPDH expression as an internal standard . ^^^ In contrast , artemin , GDNF , GFRalpha 1 3 and Ret RNA expression were strongly upregulated in the auditory nerve following deafness , indicating their importance in protecting the auditory nerve against cell damage . . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
In this immunohistochemical study , we localized GDNF , neurturin , GFRalpha 1 , GFRalpha 2 and Ret in the adult rat ON and olfactory bulb . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GDNF induced OECs migration was demonstrated depending on GFRalpha 1 and Ret receptor , and activation of JNK and Src signaling cascades . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Recently , a receptor complex has been identified for GDNF that includes the Ret tyrosine kinase receptor and a glycosylphosphatidylinositol linked protein termed `` GDNFRalpha . ' ' However , differences in the phenotype of Ret and GDNF knockout animals suggest that Ret has at least one additional ligand . ^^^ NTN also caused Ret phosphorylation in fibroblasts that were transfected stably with Ret and GDNFRalpha but not in cells expressing Ret alone . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The messenger RNAs for both glial cell line derived neurotrophic factor receptors , c ret and GDNFRalpha , are induced in the rat brain in response to kainate induced excitation . ^^^ Glial cell line derived neurotrophic factor ( GDNF ) has two receptors , receptor tyrosine kinase c ret and glycosylphosphatidylinositol linked cell surface receptor GDNFRalpha . ^^^ Here we show that systemic kainate induced excitation leads to a transient increase of both c ret and GDNFRalpha messenger RNAs in the rat brain . ^^^ Northern analysis demonstrated that , in the hippocampus , the maximal 2 . 5 fold increase of c ret and four fold increase of GDNFRalpha messenger RNAs was observed after 12 h of kainate injection , in contrast to GDNF messenger RNA , which reaches its maximum in 4 6 h . ^^^ GDNFRalpha and c ret show distinct , but partially overlapping , patterns of expression in the brain after kainate treatment . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
The transcription factors Wt 1 and Eya 1 , the signalling molecules Gdnf and LIF and the receptors c Ret and GdnfRalpha have been demonstrated to fulfil fundamental roles in the first step of metanephric induction , the outgrowth of the ureter . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Glial cell line derived neurotrophic factor ( Gdnf ) and its alpha receptor ( Gfra 1 ) interact with the Ret receptor triggering its tyrosine kinase activity . ^^^ As Gdnf and Ret have been linked to the development of Hirschsprung disease ( HSCR ) , it seems likely that Gfra 1 could also be a susceptibility gene for HSCR . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
We also analyzed markers located close to several candidate genes ( RET , NF 1 , GDNF , GFRA 1 , EDNRB , and EDN 3 ) involved to a different extent in other neurocristopathies . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
We studied the RET , GDNF , GFRA 1 , PHOX2A , PHOX2B , HASH 1 , EDN 1 , EDN 3 , EDNRB , and BDNF genes in seven patients with isolated CCHS and three patients with HSCR . ^^^ We also found several mutations of the RET , GFRA 1 , PHOX2A , and HASH 1 genes in patients with or without mutations of the PHOX2B gene . ^^^ Mutations of the RET , GFRA 1 , PHOX2A , and HASH 1 genes may also be involved in the pathogenesis of CCHS . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
Enteric neurons are eliminated after injection with antisense morpholino oligonucleotides against ret or against both Gfra 1 orthologs , but are not affected by antisense oligonucleotides against gfra 2 . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
GFRA 1 and RET expression was identified in a subset of gonocytes at birth , was restricted to SSCs during normal spermatogenesis , and RET expressing cells were abundant in a cryptorchid model of SSC self renewal . ^^^ We used the whole testis transplantation technique to overcome the limitation of neonatal lethality of Gdnf , Gfra 1 , and Ret deficient mice and found that each of these genes is required for postnatal spermatogenesis and not for embryological testes development . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
RET and GFRA 1 germline polymorphisms in medullary thyroid cancer patients ] . ^^^ The role of RET and GFRA 1 germline polymorphisms in predisposition to sporadic medullary thyroid cancer ( MTC ) and polymorphisms ' modulation effect on clinical features of inherited and sporadic MTC were investigated . ^^^ Screening of RET exons and portion of introns 1 , 8 , 10 , 13 , 14 , 15 , 16 and GFRA 1 5 ' UTR was performed by means of direct sequencing and PCR RFLP . 8 polymorphic variants of RET gene ( exons 11 , 13 , 14 , 15 and introns 1 , 8 , 13 , 14 ) and 4 GFRA 1 polymorphisms in GFRA 1 were detected . ^^^
Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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Interacting proteins: P56159 and P07949	Pubmed	SVM Score :0.0
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