| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.51294428 |
| Mutation analysis of glial cell line derived neurotrophic factor ( GDNF ) , a ligand for the RET / GDNF receptor alpha complex , in sporadic phaeochromocytomas . 0.51294428^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :1.2991834 |
| 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 . 1.2991834^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.58261272 |
| GDNFR alpha binds GDNF specifically and mediates activation of the Ret protein tyrosine kinase ( PTK ) . 0.58261272^^^ Treatment of Neuro 2a cells expressing GDNFR alpha with GDNF rapidly stimulates Ret autophosphorylation . 0.52011271^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :1.7483296 |
| 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 . 1.7483296^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.7275221 |
| We further demonstrate that NTNR alpha binds NTN ( K [ d ] approximately 10 pM ) but not GDNF with high affinity ; that GDNFR alpha binds to GDNF but not NTN with high affinity ; and that cellular responses to NTN require the presence of NTNR alpha . 0.7275221^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.75589071 |
| GDNF binds to GDNFR alpha and this complex , in turn , is believed to interact with the RET receptor tyrosine kinase to effect downstream signalling . 0.75589071^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.56213451 |
| 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 . 0.56213451^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.69835246 |
| GDNF preferentially binds to GFRalpha 1 which then interacts with the receptor tyrosine kinase RET . 0.69835246^^^ Mutation and deletion analysis of GFR alpha 1 , encoding the co receptor for the GDNF / RET complex , in human brain tumours . 0.55565348^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.75358501 |
| GDNF binds with high affinity to GDNF family receptor alpha 1 ( GFR alpha 1 ) . 0.75358501^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.84579308 |
| GDNF binds with high affinity to the GDNF family receptor alpha 1 ( GFRalpha 1 ) , which is highly expressed in the midbrain . 0.84579308^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.84233201 |
| GDNF binds with high affinity to the GDNF family receptor alpha 1 ( GFRalpha 1 ) which is expressed in different brain areas . 0.84233201^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.84300063 |
| In cells lacking RET , GDNF binds with high affinity to the NCAM and GFRalpha 1 complex , which activates Fyn and FAK . . 0.84300063^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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 ) . ^^^ Complementary and overlapping expression of glial cell line derived neurotrophic factor ( GDNF ) , c ret proto oncogene , and GDNF receptor alpha indicates multiple mechanisms of trophic actions in the adult rat CNS . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| The potential receptor mediating the pleiotropic effects of glial cell line derived neurotrophic factor has been characterized only recently as a novel glycosyl phosphatidylinositol linked protein , GDNFR alpha . ^^^ Because GDNFR alpha is a cell surface receptor , an additional protein ( s ) was thought to be involved in the glial cell line derived neurotrophic factor signalling cascade . ^^^ 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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Cloning , mRNA distribution and chromosomal localisation of the gene for glial cell line derived neurotrophic factor receptor beta , a homologue to GDNFR alpha . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Neurturin and glial cell line derived neurotrophic factor receptor beta ( GDNFR beta ) , novel proteins related to GDNF and GDNFR alpha with specific cellular patterns of expression suggesting roles in the developing and adult nervous system and in peripheral organs . ^^^ Cloning strategies were used to identify a gene termed glial cell line derived neurotrophic factor receptor beta ( GDNFR beta ) related to GDNFR alpha . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| The receptor for glial cell line derived neurotrophic factor ( GDNF ) consists of GFRalpha 1 and Ret . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| We report the identification of an additional member of the glial cell line derived neurotrophic factor ( GDNF ) family receptor , termed GFRalpha 3 , that is homologous to the previously identified GDNF and neurturin ligand binding receptors GFRalpha 1 and GFRalpha 2 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Neurturin and glial cell line derived neurotrophic factor ( GDNF ) promote the survival and maintenance of different types of neuronal cells and signal through a receptor complex composed of a ligand binding subunit , either GDNF family receptor alpha 1 ( GFRalpha 1 ) or alpha 2 ( GFRalpha 2 ) , together with the cRET membrane bound protein tyrosine kinase . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Glial cell line derived neurotrophic factor ( GDNF ) mediates signaling across the cell membrane by interaction with the RET GDNFR alpha receptor complex . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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 ) . ^^^ Glial cell line derived neurotrophic factor / neurturin induced differentiation and its enhancement by retinoic acid in primary human neuroblastomas expressing c Ret , GFR alpha 1 , and GFR alpha 2 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Glial cell line derived neurotrophic factor ( GDNF ) mediates neuronal survival through a receptor complex composed of the c Retproto oncogene and GFR alpha 1 , a member of a family of GPI anchored receptors . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| 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: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| We report here the identification of a gene , termed GFRalpha 3 ( glial cell line derived neurotrophic factor family receptor alpha 3 ) , related to GFRalpha 1 and GFRalpha 2 ( also known as GDNFR alpha and GDNFR beta ) , and describe distribution of GDNFalpha 3 in the nervous system and other parts of the mouse body during development and in the adult . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Expression of glial cell line derived neurotrophic factor and GDNFR alpha mRNAs in human peripheral neuropathies . ^^^ 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: P39905 and P56159 |
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 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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: P39905 and P56159 |
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 ) . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| 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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| We here report that the glial cell line derived neurotrophic factor ( GDNF ) receptor GFRalpha 1 mRNA and GFRalpha 1 protein like immunoreactivity are upregulated in spinal motoneurons , and in dorsal root ganglion neurons of 30 month old rats . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| First , immunohistochemical examination of the cerebral cortex of rats revealed that glial cell line derived neurotrophic factor receptor ( GFRalpha 1 ) was preferentially expressed on the cell membranes of capillary endothelial cells . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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: P39905 and P56159 |
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 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Constitutive loss of Ret , its co receptor gfralpha 1 , or the ligand glial cell line derived neurotrophic factor results in renal agenesis . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Glial cell line derived neurotrophic factor ( GDNF ) and its receptor ( GFR alpha 1 ) are strongly expressed in human gliomas . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Glial cell line derived neurotrophic factor receptor alpha 1 ( GFRalpha 1 , also known as GDNFR alpha ) is a glycolipid anchored membrane protein of the GFRalpha family , which binds glial cell line derived neurotrophic factor [ Jing S . et al . ( 1996 ) Cell 85 , 1113 1124 ; Treanor J . ^^^ 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 . ^^^ Moreover , neuroprotective actions of exogenous glial cell line derived neurotrophic factor also require full GFRalpha 1 receptor expression . . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Glial cell line derived neurotrophic factor ( GDNF ) , neurturin ( NTN ) , and their receptors , GDNF family receptor alpha 1 ( GFRalpha 1 ) and GDNF family receptor alpha 2 ( GFRalpha 2 ) , are critically important for kidney and nervous system development . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| The localization of glial cell line derived neurotrophic factor ( GDNF ) family receptor alpha 1 ( GFRalpha 1 ) was investigated in rat brain by immunohistochemistry using a polyclonal antibody against a specific sequence of the rat protein . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| As one of the target derived trophic factors , glial cell line derived neurotrophic factor ( GDNF ) has been shown to exert its effects on motor neurons via a receptor complex including GDNF receptor alpha 1 ( GFR alpha 1 ) . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| 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 ) . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Two related ligands , glial cell line derived neurotrophic factor ( GDNF ) and neurturin ( NRTN ) , are expressed by Sertoli cells , but their cognate ligand binding co receptors , GDNF family receptor alpha 1 and alpha 2 , are displayed by different germ cells suggesting different targets for the ligands . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Glial cell line derived neurotrophic factor ( GDNF ) and its receptors GFRalpha 1 and GFRalpha 2 in the human testis . ^^^ Glial cell line derived neurotrophic factor ( GDNF ) and its receptors GFRalpha 1 and GFRalpha 2 were found in the human testis during fetal development ( 15 34 weeks of gestation ) and in adult men ( 51 86 years of age ) by means of RT PCR , immunohistochemistry and Western blot techniques . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| In the present study we localized glial cell line derived neurotrophic factor ( GDNF ) , and the high affinity receptor for GDNF ( GFRalpha 1 ) in the rat retina . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| The expression and localization of glial cell line derived neurotrophic factor ( GDNF ) and its receptor GFR alpha 1 in the testis were examined , because the blood testis barrier is a well known tissue barrier and we previously reported that GDNF reduced the endothelial permeability of the blood brain barrier ( BBB ) . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Here we demonstrated that during the course of postnatal development , nerve injury induced down regulation of the glial cell line derived neurotrophic factor ( GDNF ) receptor GFRalpha 1 in axotomized hypoglossal motoneurons of rat are gradually converted to the adult up regulation pattern of response . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Ledda et al . , in this issue of Neuron , demonstrate that the target derived receptor glial cell line derived neurotrophic factor receptor alpha 1 ( GFRalpha 1 ) can also act in trans as an axon guidance molecule for neurons . . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| We investigated the agonistic activities of N ( 4 ) ( 7 chloro 2 [ ( E ) 2 ( 2 chloro phenyl ) vinyl ] quinolin 4 yl ) N ( 1 ) , N ( 1 ) diethyl pentane 1 , 4 diamine ( XIB 4035 ) , at the glial cell line derived neurotrophic factor ( GDNF ) family receptoralpha 1 ( GFRalpha 1 ) in Neuro 2A cells , a mouse neuroblastoma cell line which is a suitable model for investigating functions mediated through GFRalpha 1 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| The binding of human glial cell line derived neurotrophic factor to heparin and heparan sulfate : importance of 2 O sulfate groups and effect on its interaction with its receptor , GFRalpha 1 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| We have investigated the role of glial cell line derived neurotrophic factor ( GDNF ) and the effect of soluble or immobilized localization of its GDNF family receptor alpha 1 ( GFRalpha 1 ) on neurite growth in cultured embryonic Bax ( / ) dorsal root ganglion neurons , which survive in the absence of trophic support . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Possible involvement of glial cell line derived neurotrophic factor and its receptor , GFRalpha 1 , in survival and maturation of thymocytes . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Glial cell line derived neurotrophic factor receptor GFRalpha 1 is expressed in the rat striatum during postnatal development . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Analysis of the expression of the glial cell line derived neurotrophic factor ( GDNF ) and its receptors GFRalpha 1 , GFRalpha 2 , and GFRalpha 3 using triple immunofluorescence and confocal laser scanning microscopy revealed that in all animals showing marked hippocampal DND , the neuronal staining for GFRalpha 1 , GFRalpha 3 , and GDNF decreased prior to the onset of TUNEL staining in CA 1 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| The GDNF ( glial cell line derived neurotrophic factor ) binding receptor GFRalpha 1 ( GDNF family receptor alpha 1 ) is attached to the membrane by a GPI ( glycosylphosphatidylinositol ) anchor and consists of three cysteine rich domains . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Moreover , the cells expressed detectable levels of protein markers specific for germ cells such as Dazl , and specific for germ line stem cells such as Oct 4 , a transcription factor , and GFRalpha 1 , the receptor for glial cell line derived neurotrophic factor ( GDNF ) . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| We show in the present study that GFR alpha 1 , the receptor for GDNF ( glial cell line derived neurotrophic factor ) , is strongly expressed by a subset of type A spermatogonia in the basal part of the seminiferous epithelium . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Glial cell line derived neurotrophic factor ( GDNF ) receptor alpha 1 ( GFR alpha 1 ) is highly selective for GDNF versus artemin . ^^^ To clarify whether glial cell line derived neurotrophic factor ( GDNF ) receptor alpha 1 ( GFRalpha 1 ) , the glycosylphosphatidylinositol ( GPI ) linked coreceptor for GDNF , is also a functional coreceptor for artemin ( ART ) , we have studied receptor binding , signaling , and neuronal survival . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Expression of glial cell line derived neurotrophic factor ( GDNF ) and GDNF family receptor alpha 1 in mouse taste bud cells after denervation . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Glial cell line derived neurotrophic factor ( GDNF ) exerts its effect through a multi component receptor system consisting of GFRalpha 1 , RET and NCAM . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Using immunomagnetic cell sorting , testis cells were selected for the expression of alpha ( 6 ) integrin , alpha ( 5 ) integrin , c kit receptor tyrosine kinase ( Kit ) , or a binding subunit of glial cell line derived neurotrophic factor ( GDNF ) receptor , GFRalpha 1 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Here , we show that glial cell line derived neurotrophic factor ( GDNF ) is produced in the olfactory bulb but distributed along the rostral migratory stream ( RMS ) in a pattern concordant with the expression of its GPI anchored receptor GFRalpha 1 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| The majority of Ret+ are double labeled for GFRalpha 1 and glial cell line derived neurotrophic factor ( GDNF ) . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Neurturin and glial cell line derived neurotrophic factor ( GDNF ) are neurotrophic factors for penile parasympathetic neurons , so we also examined expression of relevant receptors , GFRalpha 1 and GFRalpha 2 , in injured pelvic ganglion neurons . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| SSCs from KM pups could be cultured on MEF feeders in StemPro 34 SFM Medium supplemented with glial cell line derived neurotrophic factor ( GDNF ) , soluble GDNF family receptor alpha 1 ( GFRa 1 ) and basic fibroblast growth factor ( bFGF ) for 1 month . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Here we show that physiological responses to GDNF require the presence of a novel glycosyl phosphatidylinositol ( GPI ) linked protein ( designated GDNFR alpha ) that is expressed on GDNF responsive cells and binds GDNF with a high affinity . ^^^ 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: P39905 and P56159 |
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 . ^^^ Fibroblasts expressing TrnR 2 and Ret are approximately 30 fold more sensitive to NTN than to GDNF treatment , whereas those expressing TrnR 1 and Ret respond equivalently to both factors , suggesting the TrnR 2 Ret complex acts preferentially as a receptor for NTN . ^^^ Comparative analysis of TrnR 1 , TrnR 2 , and Ret expression indicates that multiple receptor complexes , capable of mediating GDNF and NTN signaling , exist in vivo . . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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: P39905 and P56159 |
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 . ^^^ In addition , GDNF and GFRalpha 1 transcripts were seen in the preodontoblasts and odontoblasts , suggesting that they may be involved in differentiation and maintenance of functional properties of the odontoblasts . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Two accessory molecules denoted GDNF family receptor 1 and 2 ( GFRalpha 1 and GFRalpha 2 ) have been described that function in GDNF and neurturin signaling complexes . ^^^ 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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Assignment of the GDNF family receptor alpha 1 ( GFRA 1 ) to human chromosome band 10q26 by in situ hybridization . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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 . ^^^ GDNFR alpha and GDNFR beta together form a new family of GPI linked receptors for GDNF like molecules . . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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 ) . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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 . ^^^ After a sciatic nerve crush a rapid increase in GDNF mRNA was observed in the distal part of the nerve and a delayed elevation in the muscle , while GDNFR alpha mRNA was up regulated in the distal part of the sciatic nerve but not in proximal nerve or spinal cord . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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: P39905 and P56159 |
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 . ^^^ These data suggest that GFRA 1 ' S role in enteric neurogenesis in humans remains to be elucidated and that RET signaling in the gut may take place via alternate pathways , such as the recently described GDNF related molecule neurturin and its GFRA 1 like coreceptor , GFRA2 . . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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 . ^^^ All the neurotrophin mRNAs and GDNF mRNAs were significantly elevated in the diseased nerves and their expression levels well correlated to the extent of T cell and macrophage invasion . p 75 and GDNFR alpha mRNAs were upregulated in correlation to the extent of axonal degeneration . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| However , these cells did not express the mRNA for GDNFRalpha , the other component of the GDNF receptor complex . . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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 . ^^^ 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: P39905 and P56159 |
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 . ^^^ GFRalpha 1 is an essential receptor component for GDNF in the developing nervous system and kidney . ^^^ GFRalpha 1 deficient dopaminergic and nodose sensory ganglia neurons no longer respond to GDNF or to the structurally related protein neurturin ( NTN ) but can be rescued when exposed to GDNF or neurturin in the presence of soluble GFRalpha 1 . ^^^ 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: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| The similarity in potency and efficacy of NTN and GDNF on DA neurons in several paradigms stands in contrast to the differential distribution of the receptor components GDNF Family Receptor alpha 1 ( GFRalpha 1 ) and GFRalpha 2 within the ventral mesencephalon . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| GFRalpha 1 , GFRalpha 2 , and GFRalpha 3 constitute a family of structurally related , glycosyl phosphatidylinosital linked , cell surface proteins , two of which , GFRalpha 1 and GFRalpha 2 , are components of the receptor complex for the neurotrophic factors GDNF and neurturin , respectively . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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 most likely act as GDNF receptors in colon but may have alternative ligands in other enteric segments . . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Age dependent differences in the effects of GDNF and NT 3 on the development of neurons and glia from neural crest derived precursors immunoselected from the fetal rat gut : expression of GFRalpha 1 in vitro and in vivo . ^^^ GDNF increased the number of neurons anchoring GFRalpha 1 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Expression of GDNF receptor ( RET and GDNFR alpha ) mRNAs in the spinal cord of patients with amyotrophic lateral sclerosis . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Forebrain ischaemia induced elevated expression of GDNF mRNA in dentate granule cells , GFRalpha 1 mRNA in the dentate granule cell layer , hilus and CA 3 pyramidal layer , and GFRalpha 2 mRNA in the parietal cortex . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Expression of GDNF and GDNFR alpha mRNAs in human peripheral neuropathies ] . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Furthermore , OLI neu and OLN 93 cells expressed transcripts encoding the GDNF receptors Ret and GFRalpha 1 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Neurons that were more sensitive to GDNF expressed higher levels of GFRalpha 1 mRNA than GFRalpha 2 mRNA and neurons that were more sensitive to neurturin expressed higher levels of GFRalpha 2 mRNA than GFRalpha 1 mRNA . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Expression of GDNF and GDNFR alpha mRNAs in muscles of patients with motor neuron diseases . ^^^ 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 ) . ^^^ In situ hybridization study revealed that GDNF and GDNFR alpha mRNAs were localized in subsarcolemmal space of muscle cells . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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: P39905 and P56159 |
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: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| The changes in GFRalpha 1 and GFRalpha 2 expression after axotomy could be largely reversed by treatment with GDNF . . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Tissue distributions of their respective receptors , GFR alpha 1 and GFR alpha 2 , reveal overlapping but distinct patterns of expression , which implies that the in vivo actions of GDNF and NTN may be different . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| At early stages of development both the GDNF receptor , gfralpha 1 , and the neurturin ( NTN ) receptor , gfralpha 2 , were expressed in the oculomotor , facial and spinal accessory , and only gfralpha 1 in the trochlear , superior salivatory , trigeminal , hypoglossal and weakly in the dorsal motor nucleus of the vagus and the ambiguous nucleus . ^^^ A motor neuron subnuclei specific expression of gfralpha 1 and gfralpha 2 was seen in the facial and trigeminal nuclei which corresponded to their dependence on GDNF in null mutant mice . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Whereas the GFRalpha 1 transcripts were detected at similar levels in normal tissues and in tumors , GDNF was frequently found expressed in sporadic tumors at levels several times higher than in controls . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Consequently , we found that RA alone induced the responsiveness of SCG neurons specifically to GDNF by upregulating the ligand specifying receptor for GDNF ( GFRalpha 1 ) at both the mRNA and protein levels . ^^^ On the other hand , BMP 2 , which had no significant effect by itself on the GDNF responsiveness , promoted the action of RA to upregulate GFRalpha 1 and enhance the GDNF responsiveness . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| GDNF signaling is mediated through a two component system consisting of the so called GDNF receptor alfa ( GFRalpha 1 ) which binds to GDNF . ^^^ 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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Binding of GDNF and neurturin to human GDNF family receptor alpha 1 and 2 . ^^^ We show that the rate of dissociation of ( 125 ) 1 GDNF from GFRalpha 1 is increased in the presence of 50 nm GDNF , an effect that can be explained by the occurrence of negative cooperativity . ^^^ A high affinity site with a K ( D ) of 11 pm for ( 125 ) 1 GDNF is detected only when GFRalpha 1 is co expressed with cRET at a DNA ratio of 1 : 3 . ^^^ These results suggest an interaction of GFRalpha 1 and cRET in the absence of GDNF and demonstrate that the high affinity binding can be measured only when cRET is present . . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Following transaction of the sciatic nerve GDNF mRNA was up regulated rapidly in the denervated nerve distal to the cut along with the mRNA for one of its receptors , GFRalpha 1 . ^^^ GFRalpha 1 mRNA was also increased in the DRG ipsilateral to the nerve injury suggesting that GDNF may be involved in the trophic support of DRG sensory neurons . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Broad specificity of GDNF family receptors GFRalpha 1 and GFRalpha 2 for GDNF and NTN in neurons and transfected cells . ^^^ The binding of soluble GFRalphas to transfected cells suggested that different GFRalphas were dedicated to particular ligands , with GDNF acting primarily or entirely through GFRalpha 1 , and neurturin ( NTN ) , through GFRalpha 2 . ^^^ By biochemical and genetic addition and / or deletion of GFRalpha 1 and 2 , we show that in both neuronal cell types , robust biological activities of GDNF or NTN can be mediated by either GFRalpha 1 or GFRalpha 2 , although GDNF is slightly more potent in dopaminergic ( DA ) neurons which normally express GFRalpha 1 , and NTN in submandibular neurons which normally express GFRalpha 2 . ^^^ Throughout the body , GDNF and NTN are likely to have important biological actions on both GFRalpha 1 and GFRalpha 2 expressing cells . . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| They bind to a specific membrane anchored GDNF family receptor as follows : GFRalpha 1 for GDNF , GFRalpha 2 for neurturin , GFRalpha 3 for enovin / artemin , and ( chicken ) GFRalpha 4 for persephin . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| The DNA sequences of 5 further genes ( GDNF , GDNFRalpha , EDN 3 , EDNRB , and NTN ) , that may contribute to the development of HSCR , have not shown mutations in the patients analyzed so far . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Thus , GFRalpha 1 , but not GFRalpha 2 , is absolutely required for the survival response of a majority of motoneurons to both GDNF and NTN . ^^^ Most motoneurons purified from Gfra 1 null mutant mice had lost their responsiveness to both GDNF and NTN . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Reactive astrocytes of the quinolinic acid lesioned rat striatum express GFRalpha 1 as well as GDNF in vivo . ^^^ Therefore , the present follow up experiment was performed with the aims : ( 1 ) to look at GDNF expression in the QA injected striatum at 28 days , ( 2 ) to look for possible immunohistochemical expression of GFRalpha 1 in the QA injected striatum at the same observation time , and ( 3 ) to use confocal microscopy of double immunofluorescence labeling of glial cell specific markers to identify the cell types expressing GDNF and GFRalpha 1 in the striatum at 28 days following a QA injection . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Expression of GFRalpha 1 , receptor for GDNF , in rat brain capillary during postnatal development of the BBB . ^^^ In the present study , we examined the relation between permeability of the BBB , using Evans blue as a tracer , and expression of the GDNF family receptor ( GFRalpha 1 ) during postnatal development of the BBB . ^^^ 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 . ^^^ The reciprocal relation between GFRalpha 1 expression and the permeability of the BBB strongly suggests active participation of GDNF in postnatal development of the BBB , although the mechanism ( s ) involved is still veiled . . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| GDNF and GFRalpha 1 are components of the axolotl pronephric duct guidance system . ^^^ 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 . ^^^ We provide evidence that GDNF signaling through GFRalpha 1 is sufficient to direct pathfinding of migrating pronephric duct cells in axolotl embryos by : ( 1 ) demonstrating that application of soluble GFRalpha 1 to an embryo lacking all GPI linked proteins rescues PND migration in a dose dependent fashion , ( 2 ) showing that application of excess soluble GFRalpha 1 to a normal embryo inhibits migration and that inhibition is dependent upon GDNF binding activity , and ( 3 ) showing that the PND will migrate toward a GDNF soaked bead in vivo , but will fail to migrate when GDNF is applied uniformly to the flank . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| The timing of this shift corresponded to developmental changes in gut expression of GFR alpha 1 , a co receptor in the GDNF Ret signaling complex . ^^^ GFR alpha 1 could participate in GDNF signaling when expressed in cis on the surface of enteric precursor cells , or as a soluble protein . ^^^ The GDNF mediated response was greater when cell surface , compared with soluble , GFR alpha 1 was present , with the maximal response seen the presence of both cis and trans forms of GFR alpha 1 . ^^^ In addition to contributing to GDNF signaling , cell surface GFR alpha 1 modulated the specificity of interactions between GDNF and soluble GFR alphas . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Distinct hydrophobic and positively charged residues in this central region were required for binding of GFRalpha 1 to GDNF . ^^^ Interaction of GFRalpha 1 and GFRalpha 2 with GDNF and neurturin required distinct subsegments within this central domain , which allowed the construction of chimeric receptors that responded equally well to both ligands . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| The aim of the present study was to knockdown GDNF , its receptor GFR alpha 1 , and the related family member persephin by using antisense oligonucleotides and to observe the effects on cell proliferation . ^^^ This protocol markedly reduced GDNF and GFR alpha 1 protein levels in C 6 glioma cells compared with control oligonucleotides . ^^^ Knockdown of C 6 cells with GDNF and GFR alpha 1 but not with persephin antisense oligonucleotides significantly decreased the number of C 6 glioma cells and also inhibited the incorporation of bromodeoxyuridine as a sign of reduced DNA synthesis . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Although both c Ret and GFRalpha 1 are required for responsiveness to GDNF , GFRalpha 1 is widely expressed in the absence of c Ret , suggesting alternative roles for `` ectopic ' ' sites of GFRalpha 1 expression . ^^^ These results provide an explanation for the tissue distribution of GFRalpha 1 , supporting the physiological importance of c Ret activation in trans as a novel mechanism to potentiate and diversify the biological responses to GDNF . . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| GFRalpha 1 , GFRalpha 2 , GFRalpha 3 and GFRalpha 4 are the physiological coreceptors for GDNF , neurturin , artemin and persephin , respectively . ^^^ 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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| GDNF signals via GFRalpha 1 , neurturin via GFRalpha 2 , artemin via GFRalpha 3 , whereas the mammalian GFRalpha receptor for persephin ( PSPN ) is unknown . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| In the present study , we immunohistochemically examined the expression of GDNF , neurturin ( NTN ) and their receptors , GFRalpha 1 for GDNF and GFRalpha 2 for NTN , because the capillaries of the inner BRB show specialization very similar to the blood brain barrier ( BBB ) . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| We have identified zebrafish orthologues of glial cell line derived neurotrophic factor ( GDNF ) and the ligand binding component of its receptor GFRalpha 1 . ^^^ In the zebrafish PMN , GFRalpha 1 is only expressed in the CaP motor neuron while GDNF is expressed in the ventral somitic muscle that it innervates . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 ) . ^^^ Thus , spinal motoneurons are highly heterogeneous in their expression of receptors for neurotrophic factors of the GDNF family , but their differing responses to NTN are not correlated with expression levels of Gfra 1 or Gfra2 . . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Presence of GDNF messenger ( m ) RNA and receptors GFRalpha 1 and GFRalpha 2 mRNA was analyzed by reverse transcription polymerase chain reaction . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| The biological effects of GDNF are mediated by GDNF family receptor alpha 1 ( GFRalpha 1 ) and c Ret . ^^^ Since GDNF is neuroprotective , up regulation of GFRalpha 1 and c Ret could enhance the responsiveness to GDNF and reduce neuronal damage . ^^^ The selective up regulation of GFRalpha 1 and c Ret in different brain areas suggests that there may be regional differences in GDNF induced neuroprotection in stroke . . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ Thus , adrenal medullary cells express mRNAs for the GDNF receptor components Ret and GFRalpha 1 , increase their expression upon being cultured in serum containing medium and respond to GDNF treatment with an increase in the number of cells that develop nerve processes . . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Co stimulation with a soluble form of the GFRalpha 1 co receptor potentiated ligand dependent phosphorylation of different intracellular tyrosines to a similar extent and increased the survival of superior cervical ganglion neurons compared with treatment with GDNF alone . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ In addition , these observations reveal that c Ret independent signaling of GFRalpha 1 is ligand specific and occurs only with GDNF . . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| The mRNAs for receptors GFRalpha 1 and GFRalpha 2 were upregulated only after maximal GDNF upregulation and remained elevated as late as 6 months . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| RET ( Men2B ) transgene produces sympathoadrenal tumors but does not prevent intestinal aganglionosis in gdnf / or gfr alpha 1 ( / ) mice . ^^^ The ligand , GDNF , stimulates RET activity through a co receptor , GFR alpha 1 . ^^^ 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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ METHODS : The levels of GDNF , GDNFR alpha and GDNFR beta mRNA were assayed by reverse transcription polymerase chain reaction ( RT PCR ) with the beta actin mRNA as an internal control . ^^^ RESULTS : The GDNF mRNA levels were increased , and GDNFR alpha and GDNFR beta mRNA levels was slightly increased in the spinal cord and brainstem during morphine dependence . ^^^ While the GDNF , GDNFR alpha and GDNFR beta levels in the frontal cortex were increased significantly at 1 , 2 and 4 h after the injection of naloxone during morphine withdrawal . ^^^ The pre treatment with L N nitric arginine methylester ( 10 mg / kg ) , the expressions of GDNF and GDNFR beta in the spinal cord , both GDNFR alpha and GDNFR beta in the frontal cortex were decreased . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Expression of GDNF and its preferred receptor , GDNF family receptor alpha 1 ( GFRalpha 1 ) , was transiently up regulated by quinolinate and kainate , but with differing intensity and temporal pattern . ^^^ Immunohistochemical analysis showed that , although GDNF and GFRalpha 1 were initially localized in neurons , excitotoxicity induced the expression of these proteins in astrocyte like cells . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Glial derived neurotropic factor ( GDNF ) signaling is mediated through a 2 component system consisting of the so called GDNF receptor alpha ( GFRalpha 1 ) , which binds to GDNF . ^^^ 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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Interestingly , we found that tyrosine hydroxylase ( TH ) positive neurons in the LC express both GFRalpha 1 and 2 receptors in a developmentally regulated fashion , suggesting a function for their preferred ligands : GDNF and NTN , respectively . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| We found that such neuroprotective effects are mediated through specific GDNF receptor alpha 1 ( GFRalpha 1 ) . ^^^ Animals with a deficiency in GFRalpha 1 have less GDNF induced neuroprotection . ^^^ These . data suggest that GDNF can protect against ischemic injury through a GFRalpha 1 / NOS mechanism . ^^^ We also found that the receptor for GDNF , GFRalpha 1 , and its signaling moiety c Ret were upregulated , starting immediately after ischemia . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Endogenous GDNF and its receptor , GFRalpha 1 , were detected in GMIR 1 cells by ELISA and immunohistochemistry / Western blot , respectively . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Genetic analysis of RET , GFR alpha 1 and GDNF genes in Spanish families with multiple endocrine neoplasia type 2A . ^^^ This locus encodes a receptor tyrosine kinase whose activation requires the formation of a multimeric receptor complex including GDNF as a ligand and GFR alpha 1 as a coreceptor . ^^^ 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 ) . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Analysis of MN survival in GFRalpha 1 ( / ) mice demonstrated that the trophic effect of GDNF was completely mediated by its preferred coreceptor , GDNF family receptor alpha 1 ( GFRalpha 1 ) . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| TGFbeta induces GDNF responsiveness in neurons by recruitment of GFRalpha 1 to the plasma membrane . ^^^ This is supported by the fact that GDNF in the presence of a soluble GFRalpha 1 can promote survival in the absence of TGFbeta . ^^^ Our data suggest that TGFbeta is involved in GFRalpha 1 membrane translocation , thereby permitting GDNF signaling and neurotrophic effects . . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| GFRalpha 1 , a GPI anchored receptor for GDNF , is expressed as both membrane bound and secreted forms by accessory nerve cells and peripheral targets of developing sensory and sympathetic neurons during the period of target innervation . ^^^ 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 . ^^^ Soluble GFRalpha 1 prolongs GDNF mediated activation of cyclin dependent kinase 5 ( Cdk 5 ) , an event required for GFRalpha 1 induced neurite outgrowth and axon guidance . ^^^ Together with GDNF , target derived GFRalpha 1 can function in a non cell autonomous fashion as a chemoattractant cue with outgrowth promoting activity for peripheral neurons . . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| GDNF and NRTN bind to the tyrosine kinase receptor Ret and the receptors GFRalpha 1 and GFRalpha 2 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ GDNF promotes tubulogenesis of GFRalpha 1 expressing MDCK cells by Src mediated phosphorylation of Met receptor tyrosine kinase . ^^^ GDNF can also signal independently of Ret via GFRalpha 1 , although the mechanism has remained unclear . ^^^ In MDCK cells expressing GFRalpha 1 but no Ret , GDNF stimulates branching but not chemotactic migration , whereas both branching and chemotaxis are promoted by GDNF in the cells coexpressing Ret and GFRalpha 1 , mimicking HGF / Met responses in wild type MDCK cells . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Differential expression of the cell line derived neurotrophic factor ( GDNF ) receptor GFRalpha 1 in heterozygous Gfralpha 1 null mutant mice after stroke . ^^^ 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 . ^^^ Since GDNF has neuroprotective effects , the reduced up regulation of Gfralpha 1 in Gfralpha 1 ( + / ) mice at early time points after ischemia suggests that the responsiveness to GDNF and GDNF receptor mediated neuroprotection is attenuated in these genetically modified animals and may underlie their greater vulnerability . . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Glial cell derived neurothrophic factor ( GDNF ) interacts with a cell surface receptor , GFRalpha 1 , that is linked via a glycosyl phosphatidylinositol ( GPI ) lipid to the cell membrane . ^^^ 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 . ^^^ 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 . ^^^ Primary hippocampal neurons from transgenic mice that express a wild type GFRalpha 1 together with a mutant , tyrosine kinase inactive Ret also internalized GDNF efficiently ( approximately 20 % of total surface bound ligand internalized after 2 min ) . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Therefore , we examined the regulation of GDNF and its receptor ( GFR alpha 1 ) in colonic inflammation and its effects on colonic epithelial cell apoptosis . ^^^ METHODS : The expression of GDNF and GFR alpha 1 was investigated in experimental colitis of rats and in human inflammatory bowel disease ( IBD ) . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Expressions of GDNF , GDNFR alpha and Ret proteins in the brain of rats with seizures induced by pilocarpine ] . ^^^ 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 . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Interestingly , both lipopolysaccharide and TNFalpha triggered a significant decrease in the expression of the GDNF receptor , GFRalpha 1 , in glial cells . ^^^ |
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| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Identification of a surface for binding to the GDNF GFR alpha 1 complex in the first cadherin like domain of RET . ^^^ Cross linking experiments have indicated that the RETECD makes direct contacts with both the GDNF ligand and GFR alpha 1 molecule in the complex , although it has low or no detectable affinity for either component alone . ^^^ 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 . ^^^ We found that Xenopus RETECD was unable to bind to GDNF GFR alpha 1 or neurturin ( NTN ) GFR alpha 2 complexes of mammalian origin . ^^^ Subsequent loss of function experiments at higher resolution identified three small subsets of residues , mapping on the same face of the molecular model of RET CLD 1 , that were required for the interaction of human RETECD with the GDNF GFR alpha 1 complex . ^^^ |
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| Interacting proteins: P39905 and P56159 |
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 . ^^^ 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: P39905 and P56159 |
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 . ^^^ Although structural analysis of GDNF has been extensively examined , less is known about the structural basis of GFRalpha 1 function . ^^^ According to the survival and differentiation responses of these stable PC 12 cells upon GDNF stimulation and the GDNF GFRalpha 1 Ret interaction assay , residues 152NN153 , Arg 259 , and 316SNS318 in the GFRalpha 1 central region were found to be critical for GFRalpha 1 binding to GDNF and eliciting downstream signal transduction . ^^^ The single mutation R259A in the GFRalpha 1 molecule simultaneously lost its binding ability to GDNF and Ret . ^^^ These findings suggest that distinct structural elements in GFRalpha 1 may be involved in binding to GDNF and Ret . . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| CONCLUSIONS : In the course of recovery spermatogenesis , the expression of GFR alpha 1 plays a key role in turning the spermatogonial stem cell reactivity to GDNF , which promotes self renewal at a high level , or results in differentiation at a low level . . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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 ) . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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 . ^^^ GFRalpha 1 has a putative domain structure of three homologous cysteine rich domains , where domains 2 and 3 make up a central domain responsible for GDNF binding . ^^^ The structure was used to model the homologous domain 2 , the other half of the GDNF binding fragment , and to construct the first structural model of the GDNF GFRalpha 1 interaction . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Interestingly , expression of Dok 6 potentiated GDNF induced neurite outgrowth in GDNF family receptor alpha 1 ( GFRalpha 1 ) expressing Neuro2A cells that was dependent upon the C terminal residues of Dok 6 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Studies on protein phosphorylation and specific inhibitors of cell signal transduction indicate that GDNF function is mediated by receptor GFRalpha 1 and involves MAPK , cAMP / cAMP responsive element binding factor and Src kinase activities . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Expression of GDNF and GFR alpha 1 in mouse taste bud cells . ^^^ Using an immunocytochemical method , we examined whether the taste bud cells in the circumvallate papillae of normal mice expressed GDNF and its GFR alpha 1 receptor . ^^^ Using double immunostaining for either of them and NCAM , PGP 9 . 5 , or alpha gustducin , we additionally sought to determine what type of taste bud cells expressed GDNF or GFR alpha 1 , because NCAM is reported to be expressed in type 3 cells , PGP 9 . 5 , in type 3 and some type 2 cells , and alpha gustducin , in some type 2 cells . ^^^ Normal taste bud cells expressed both GDNF and GFR alpha 1 . ^^^ The percentage of GDNF immunoreactive cells among all taste bud cells was 31 . 63 % , and that of GFR alpha 1 immunoreactive cells , 83 . 21 % . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| However , other strains of mice required the addition of soluble GDNF family receptor alpha 1 and basic fibroblast growth factor to support replication . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| GDNF enhanced the phagocytic activity of the macrophages via GFRalpha 1 , glycosylphosphatidylinositol anchored specific binding site of GDNF , in a c Ret independent manner . ^^^ However , the GDNF mRNA level , but not the MCP 1 or GFRalpha 1 mRNA level , was substantially lower in the mutant macrophages than in the + / + cells irrespective of stimulation with MCP 1 or lipopolysaccharide ( LPS ) . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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 . ^^^ Optic nerve transection resulted in reduced Ret mRNA levels in retina , while the levels of GDNF , GFRalpha 1 , and 2 mRNA increased . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Using immunohistochemistry , Western blot , and RT PCR analysis techniques , the present study observed the effects of EA on the expression of GDNF and GDNF family receptor alpha 1 ( GFRalpha 1 , the high affinity receptor of GDNF ) in neuropathic pain rats . ^^^ The results showed that both protein and mRNA levels of GDNF and GFRalpha 1 in the dorsal root ganglions ( DRG ) , as well as GDNF protein in the spinal dorsal horn , were significantly increased after chronic constriction injury ( CCI ) of the rats ' sciatic nerve and could be further enhanced by EA treatment . ^^^ The present data demonstrated that EA could activate endogenous GDNF and GFRalpha 1 system of neuropathic pain rats and this might underlie the effectiveness of EA in the treatment of neuropathic pain . . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| GDNF and GFRalpha 1 promote differentiation and tangential migration of cortical GABAergic neurons . ^^^ GDNF signaling via GFRalpha 1 was found to promote the differentiation of ventral precursors into GABAergic cells , enhancing their neuronal morphology and motility . ^^^ 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 . ^^^ We conclude that one of the normal functions of GDNF signaling via GFRalpha 1 in the developing brain is to promote the differentiation and migration of cortical GABAergic neurons . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Unlike hRET , however , the extracellular domain of dRET was unable to interact with mammalian GDNF and GFRalpha 1 . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| GDNF family receptor alpha 1 phenotype of spermatogonial stem cells in immature mouse testes . ^^^ The GDNF signals through a receptor complex that includes GDNF family receptor alpha 1 ( GFRA 1 ) , which is thought to be expressed by SSCs . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| We confirmed that GDNF , GFRalpha 1 and NCAM are expressed in neonatal rat SCs . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| In branching UBs induced by whole metanephric mesenchyme cell conditioned medium , proliferating cells were localized at ampullae , where a binding receptor for GDNF , GFRalpha 1 , was found . ^^^ For example , the mRNA for the GDNF receptors , GFRalpha 1 and ret 9 , was down regulated , whereas the mRNA for collecting duct transporters , such as urea transporter 2 , aquaporin 3 , and sodium hydrogen exchanger 2 was up regulated in HRG treated UBs compared with UBs grown in the presence of branch promoting factors . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| 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: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| The present study examined the expression of GDNF and GFRalpha 1 ( the high affinity receptor of GDNF ) in dorsal root ganglions ( DRG ) in a rat model of neuropathic pain induced by chronic constriction injury ( CCI ) to the sciatic nerve . ^^^ In order to address the role of GDNF and GFRalpha 1 in neuropathic pain , antisense oligodeoxynucleotide ( ODN ) specifically against GFRalpha 1 was intrathecally administered to result in down regulation of GFRalpha 1 expression . ^^^ The results showed that both the protein and mRNA levels of GDNF and GFRalpha 1 were significantly increased after CCI , while the thermal hyperalgesia of neuropathic pain rats could be significantly aggravated by antisense ODN treatment , but not by normal saline ( NS ) or mismatch ODN treatment . ^^^ The present study demonstrated that endogenous GDNF and GFRalpha 1 might play an anti hyperalgesic role in neuropathic pain of rats . ^^^ In addition , we found a down regulation of somatostatin ( SOM ) in DRG and spinal dorsal horn after expression of GFRalpha 1 was knocked down , which suggested the possible relationship between the anti hyperalgesic effect of GDNF and GFRalpha 1 on neuropathic pain and endogenous SOM . . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| The present study was undertaken to determine whether the GDNF receptor , GFRalpha 1 , is expressed by pulpal afferents , and , further , to determine whether tooth injury evokes changes in expression of the GDNF and NGF receptors among pulpal afferents . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| In the mouse , spermatogonial stem cells express GFRalpha 1 , the receptor for GDNF , and respond to this growth factor in vivo and in vitro . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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 . ^^^ 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: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| In addition , MSCs express a variety of growth factor receptors including the glycosyl phosphatidylinositol anchored ligand binding subunit of the GDNF receptor , GFRalpha 1 , as well as fibroblast growth factor receptors one and four . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| Primer pairs specific for GDNF ( isoforms 1 and 2 ) , and its receptor molecules , GFRalpha 1 and cRET were utilized . ^^^ GDNF , cRET and GFRalpha 1 mRNA expression was clearly detected in the putamen of control and Parkinson ' s disease patients . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
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: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| The GDNF receptor GFRalpha 1 was upregulated in the SVZ 1 week after MCAO and was coexpressed with markers of dividing progenitor cells . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
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: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| The key role of GDNF and its receptor GFRalpha 1 in enteric nervous system development is conserved from zebrafish to humans . ^^^ |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P39905 and P56159 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.75358501 |
| GDNF binds with high affinity to GDNF family receptor alpha 1 ( GFR alpha 1 ) . 0.75358501^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.84579308 |
| GDNF binds with high affinity to the GDNF family receptor alpha 1 ( GFRalpha 1 ) , which is highly expressed in the midbrain . 0.84579308^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.84233201 |
| GDNF binds with high affinity to the GDNF family receptor alpha 1 ( GFRalpha 1 ) which is expressed in different brain areas . 0.84233201^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.58261272 |
| GDNFR alpha binds GDNF specifically and mediates activation of the Ret protein tyrosine kinase ( PTK ) . 0.58261272^^^ Treatment of Neuro 2a cells expressing GDNFR alpha with GDNF rapidly stimulates Ret autophosphorylation . 0.52011271^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.7275221 |
| We further demonstrate that NTNR alpha binds NTN ( K [ d ] approximately 10 pM ) but not GDNF with high affinity ; that GDNFR alpha binds to GDNF but not NTN with high affinity ; and that cellular responses to NTN require the presence of NTNR alpha . 0.7275221^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.75589071 |
| GDNF binds to GDNFR alpha and this complex , in turn , is believed to interact with the RET receptor tyrosine kinase to effect downstream signalling . 0.75589071^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.51294428 |
| Mutation analysis of glial cell line derived neurotrophic factor ( GDNF ) , a ligand for the RET / GDNF receptor alpha complex , in sporadic phaeochromocytomas . 0.51294428^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.56213451 |
| 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 . 0.56213451^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.69835246 |
| GDNF preferentially binds to GFRalpha 1 which then interacts with the receptor tyrosine kinase RET . 0.69835246^^^ Mutation and deletion analysis of GFR alpha 1 , encoding the co receptor for the GDNF / RET complex , in human brain tumours . 0.55565348^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :1.2991834 |
| 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 . 1.2991834^^^ 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 . 0.85244223^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.84300063 |
| In cells lacking RET , GDNF binds with high affinity to the NCAM and GFRalpha 1 complex , which activates Fyn and FAK . . 0.84300063^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :1.7483296 |
| 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 . 1.7483296^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 P39905 |
Pubmed |
SVM Score :0.0 |
| Assignment of the GDNF family receptor alpha 1 ( GFRA 1 ) to human chromosome band 10q26 by in situ hybridization . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Neurturin and glial cell line derived neurotrophic factor ( GDNF ) promote the survival and maintenance of different types of neuronal cells and signal through a receptor complex composed of a ligand binding subunit , either GDNF family receptor alpha 1 ( GFRalpha 1 ) or alpha 2 ( GFRalpha 2 ) , together with the cRET membrane bound protein tyrosine kinase . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 P39905 |
Pubmed |
SVM Score :0.0 |
| The similarity in potency and efficacy of NTN and GDNF on DA neurons in several paradigms stands in contrast to the differential distribution of the receptor components GDNF Family Receptor alpha 1 ( GFRalpha 1 ) and GFRalpha 2 within the ventral mesencephalon . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 . ^^^ 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 P39905 |
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 P39905 |
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 P39905 |
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 P39905 |
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 P39905 |
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 P39905 |
Pubmed |
SVM Score :0.0 |
| Glial cell line derived neurotrophic factor ( GDNF ) , neurturin ( NTN ) , and their receptors , GDNF family receptor alpha 1 ( GFRalpha 1 ) and GDNF family receptor alpha 2 ( GFRalpha 2 ) , are critically important for kidney and nervous system development . ^^^ Glial cell line derived neurotrophic factor ( GDNF ) , neurturin ( NTN ) , and their receptors , GDNF family receptor alpha 1 ( GFRalpha 1 ) and GDNF family receptor alpha 2 ( GFRalpha 2 ) , are critically important for kidney and nervous system development . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Binding of GDNF and neurturin to human GDNF family receptor alpha 1 and 2 . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 P39905 |
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 P39905 |
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 P39905 |
Pubmed |
SVM Score :0.0 |
| Two related ligands , glial cell line derived neurotrophic factor ( GDNF ) and neurturin ( NRTN ) , are expressed by Sertoli cells , but their cognate ligand binding co receptors , GDNF family receptor alpha 1 and alpha 2 , are displayed by different germ cells suggesting different targets for the ligands . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 P39905 |
Pubmed |
SVM Score :0.0 |
| Expression of GDNF and its preferred receptor , GDNF family receptor alpha 1 ( GFRalpha 1 ) , was transiently up regulated by quinolinate and kainate , but with differing intensity and temporal pattern . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Analysis of MN survival in GFRalpha 1 ( / ) mice demonstrated that the trophic effect of GDNF was completely mediated by its preferred coreceptor , GDNF family receptor alpha 1 ( GFRalpha 1 ) . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 P39905 |
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 P39905 |
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 P39905 |
Pubmed |
SVM Score :0.0 |
| We have investigated the role of glial cell line derived neurotrophic factor ( GDNF ) and the effect of soluble or immobilized localization of its GDNF family receptor alpha 1 ( GFRalpha 1 ) on neurite growth in cultured embryonic Bax ( / ) dorsal root ganglion neurons , which survive in the absence of trophic support . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 P39905 |
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 ) . ^^^ 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 P39905 |
Pubmed |
SVM Score :0.0 |
| Interestingly , expression of Dok 6 potentiated GDNF induced neurite outgrowth in GDNF family receptor alpha 1 ( GFRalpha 1 ) expressing Neuro2A cells that was dependent upon the C terminal residues of Dok 6 . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 P39905 |
Pubmed |
SVM Score :0.0 |
| However , other strains of mice required the addition of soluble GDNF family receptor alpha 1 and basic fibroblast growth factor to support replication . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| The GDNF ( glial cell line derived neurotrophic factor ) binding receptor GFRalpha 1 ( GDNF family receptor alpha 1 ) is attached to the membrane by a GPI ( glycosylphosphatidylinositol ) anchor and consists of three cysteine rich domains . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Using immunohistochemistry , Western blot , and RT PCR analysis techniques , the present study observed the effects of EA on the expression of GDNF and GDNF family receptor alpha 1 ( GFRalpha 1 , the high affinity receptor of GDNF ) in neuropathic pain rats . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 P39905 |
Pubmed |
SVM Score :0.0 |
| Expression of glial cell line derived neurotrophic factor ( GDNF ) and GDNF family receptor alpha 1 in mouse taste bud cells after denervation . ^^^ Using immunocytochemical methods , we examined whether the taste bud cells in mouse circumvallate papillae after transection of the glossopharyngeal nerves expressed GDNF and its receptor , GDNF family receptor alpha 1 ( GFRalpha 1 ) . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| GDNF family receptor alpha 1 phenotype of spermatogonial stem cells in immature mouse testes . ^^^ The GDNF signals through a receptor complex that includes GDNF family receptor alpha 1 ( GFRA 1 ) , which is thought to be expressed by SSCs . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 P39905 |
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 P39905 |
Pubmed |
SVM Score :0.0 |
| SSCs from KM pups could be cultured on MEF feeders in StemPro 34 SFM Medium supplemented with glial cell line derived neurotrophic factor ( GDNF ) , soluble GDNF family receptor alpha 1 ( GFRa 1 ) and basic fibroblast growth factor ( bFGF ) for 1 month . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Here we show that physiological responses to GDNF require the presence of a novel glycosyl phosphatidylinositol ( GPI ) linked protein ( designated GDNFR alpha ) that is expressed on GDNF responsive cells and binds GDNF with a high affinity . ^^^ 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 P39905 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 ) . ^^^ Taken together these findings indicate that GDNF , RET , and GDNFR alpha utilize multiple mechanisms to comprise physiologically relevant trophic circuits for different neuronal populations . . ^^^ 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 ) . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 P39905 |
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 P39905 |
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 P39905 |
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 . ^^^ After a sciatic nerve crush a rapid increase in GDNF mRNA was observed in the distal part of the nerve and a delayed elevation in the muscle , while GDNFR alpha mRNA was up regulated in the distal part of the sciatic nerve but not in proximal nerve or spinal cord . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ We have localized Ret messenger RNA ( mRNA ) in the developing and adult rodent and compared with to the expression of GDNF and GDNFR alpha mRNA . ^^^ 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 . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 . ^^^ 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 . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| The potential receptor mediating the pleiotropic effects of glial cell line derived neurotrophic factor has been characterized only recently as a novel glycosyl phosphatidylinositol linked protein , GDNFR alpha . ^^^ Because GDNFR alpha is a cell surface receptor , an additional protein ( s ) was thought to be involved in the glial cell line derived neurotrophic factor signalling cascade . ^^^ 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 P39905 |
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 . ^^^ Cloning , mRNA distribution and chromosomal localisation of the gene for glial cell line derived neurotrophic factor receptor beta , a homologue to GDNFR alpha . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 P39905 |
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 P39905 |
Pubmed |
SVM Score :0.0 |
| Neurturin and glial cell line derived neurotrophic factor receptor beta ( GDNFR beta ) , novel proteins related to GDNF and GDNFR alpha with specific cellular patterns of expression suggesting roles in the developing and adult nervous system and in peripheral organs . ^^^ 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 . ^^^ 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 . . ^^^ Cloning strategies were used to identify a gene termed glial cell line derived neurotrophic factor receptor beta ( GDNFR beta ) related to GDNFR alpha . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 P39905 |
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 . ^^^ GDNFR alpha and GDNFR beta together form a new family of GPI linked receptors for GDNF like molecules . . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 . ^^^ 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 P39905 |
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 . ^^^ All the neurotrophin mRNAs and GDNF mRNAs were significantly elevated in the diseased nerves and their expression levels well correlated to the extent of T cell and macrophage invasion . p 75 and GDNFR alpha mRNAs were upregulated in correlation to the extent of axonal degeneration . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ 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 . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 . . ^^^ Glial cell line derived neurotrophic factor ( GDNF ) mediates signaling across the cell membrane by interaction with the RET GDNFR alpha receptor complex . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 P39905 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ 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 . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 P39905 |
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 . ^^^ Expression of GDNF and GDNFR alpha transcripts was high at the time of explantation and remained unaffected in culture with or without RA . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ GDNF and GDNFR alpha mRNA levels were elevated to variable extent in the diseased nerves , although they were not specific to the type of diseases . ^^^ The GDNF and GDNFR alpha expression in the diseased human nerves is regulated by an underlying pathology related process , and could play a role in peripheral nerve repair . . ^^^ Expression of glial cell line derived neurotrophic factor and GDNFR alpha mRNAs in human peripheral neuropathies . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| We report here the identification of a gene , termed GFRalpha 3 ( glial cell line derived neurotrophic factor family receptor alpha 3 ) , related to GFRalpha 1 and GFRalpha 2 ( also known as GDNFR alpha and GDNFR beta ) , and describe distribution of GDNFalpha 3 in the nervous system and other parts of the mouse body during development and in the adult . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Glial cell line derived neurotrophic factor receptor alpha 1 ( GFRalpha 1 , also known as GDNFR alpha ) is a glycolipid anchored membrane protein of the GFRalpha family , which binds glial cell line derived neurotrophic factor [ Jing S . et al . ( 1996 ) Cell 85 , 1113 1124 ; Treanor J . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 . ^^^ 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 P39905 |
Pubmed |
SVM Score :0.0 |
| Expression of GDNF receptor ( RET and GDNFR alpha ) mRNAs in the spinal cord of patients with amyotrophic lateral sclerosis . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Expression of GDNF and GDNFR alpha mRNAs in human peripheral neuropathies ] . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 P39905 |
Pubmed |
SVM Score :0.0 |
| Expression of GDNF and GDNFR alpha mRNAs in muscles of patients with motor neuron diseases . ^^^ 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 ) . ^^^ In situ hybridization study revealed that GDNF and GDNFR alpha mRNAs were localized in subsarcolemmal space of muscle cells . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Immunohistochemistry revealed strong GDNF and GDNF receptor alpha 1 expressing tumor cells in human glioma tissue . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| As one of the target derived trophic factors , glial cell line derived neurotrophic factor ( GDNF ) has been shown to exert its effects on motor neurons via a receptor complex including GDNF receptor alpha 1 ( GFR alpha 1 ) . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
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 . ^^^ METHODS : The levels of GDNF , GDNFR alpha and GDNFR beta mRNA were assayed by reverse transcription polymerase chain reaction ( RT PCR ) with the beta actin mRNA as an internal control . ^^^ RESULTS : The GDNF mRNA levels were increased , and GDNFR alpha and GDNFR beta mRNA levels was slightly increased in the spinal cord and brainstem during morphine dependence . ^^^ While the GDNF , GDNFR alpha and GDNFR beta levels in the frontal cortex were increased significantly at 1 , 2 and 4 h after the injection of naloxone during morphine withdrawal . ^^^ The pre treatment with L N nitric arginine methylester ( 10 mg / kg ) , the expressions of GDNF and GDNFR beta in the spinal cord , both GDNFR alpha and GDNFR beta in the frontal cortex were decreased . ^^^ |
|
| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Expressions of GDNF , GDNFR alpha and Ret proteins in the brain of rats with seizures induced by pilocarpine ] . ^^^ 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 P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 P39905 |
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 P39905 |
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 P39905 |
Pubmed |
SVM Score :0.0 |
| Glial derived neurotropic factor ( GDNF ) signaling is mediated through a 2 component system consisting of the so called GDNF receptor alpha ( GFRalpha 1 ) , which binds to GDNF . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| The receptor for glial cell line derived neurotrophic factor ( GDNF ) consists of GFRalpha 1 and Ret . ^^^ GDNF can also bind to either GFRalpha 1 or GFRalpha 2 , and activate Ret in the presence of either binding receptor . ^^^ Although both ligands interact with both receptors , cells expressing GFRalpha 1 bind GDNF more efficiently than neurturin , while cells expressing GFRalpha 2 bind neurturin preferentially . ^^^ 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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| We report the identification of an additional member of the glial cell line derived neurotrophic factor ( GDNF ) family receptor , termed GFRalpha 3 , that is homologous to the previously identified GDNF and neurturin ligand binding receptors GFRalpha 1 and GFRalpha 2 . ^^^ We find that the gfralpha 1 population of trigeminal neurons is absent in GDNF null mutant mice , suggesting that GDNF signals in vivo by interacting with GFRalpha 1 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Two accessory molecules denoted GDNF family receptor 1 and 2 ( GFRalpha 1 and GFRalpha 2 ) have been described that function in GDNF and neurturin signaling complexes . ^^^ 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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 ) . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Glial cell line derived neurotrophic factor ( GDNF ) mediates neuronal survival through a receptor complex composed of the c Retproto oncogene and GFR alpha 1 , a member of a family of GPI anchored receptors . ^^^ Using chemical crosslinking we demonstrate here a specific interaction between GDNF and GFR alpha 2 expressed in COS cells , albeit of a lower affinity than the one between GDNF and GFR alpha 1 . ^^^ 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 . ^^^ Glial cell line derived neurotrophic factor ( GDNF ) mediates neuronal survival through a receptor complex composed of the c Retproto oncogene and GFR alpha 1 , a member of a family of GPI anchored receptors . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| GFRalpha 1 , GFRalpha 2 , and GFRalpha 3 constitute a family of structurally related , glycosyl phosphatidylinosital linked , cell surface proteins , two of which , GFRalpha 1 and GFRalpha 2 , are components of the receptor complex for the neurotrophic factors GDNF and neurturin , respectively . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| GFRalpha 1 is an essential receptor component for GDNF in the developing nervous system and kidney . ^^^ 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 . ^^^ GFRalpha 1 deficient dopaminergic and nodose sensory ganglia neurons no longer respond to GDNF or to the structurally related protein neurturin ( NTN ) but can be rescued when exposed to GDNF or neurturin in the presence of soluble GFRalpha 1 . ^^^ 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 . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 most likely act as GDNF receptors in colon but may have alternative ligands in other enteric segments . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Signaling by GDNF and NTN depends on the tyrosine kinase receptor Ret and on GFRalpha 1 and 2 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Age dependent differences in the effects of GDNF and NT 3 on the development of neurons and glia from neural crest derived precursors immunoselected from the fetal rat gut : expression of GFRalpha 1 in vitro and in vivo . ^^^ GDNF increased the number of neurons anchoring GFRalpha 1 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ 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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Forebrain ischaemia induced elevated expression of GDNF mRNA in dentate granule cells , GFRalpha 1 mRNA in the dentate granule cell layer , hilus and CA 3 pyramidal layer , and GFRalpha 2 mRNA in the parietal cortex . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 ] . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 ) . ^^^ Expression of GDNF , NTN , GFRalpha 1 and GFRalpha 2 was undetectable in THP 1 and HL 60 cells as well as in bone marrow haemopoietic cells . ^^^ In contrast , bone marrow stromal cells appeared to express GDNF , GFRalpha 1 and GFRalpha 2 but not Ret . ^^^ 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 ) . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ Strong GDNF mRNA hybridization signal , presumably restricted to Clarke ' s nucleus , was detected in the thoracic spinal cord . mRNA encoding GFRalpha 1 was expressed in the entire spinal cord gray matter with particularly high expression in the ventral horn . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Furthermore , OLI neu and OLN 93 cells expressed transcripts encoding the GDNF receptors Ret and GFRalpha 1 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Neurons that were more sensitive to GDNF expressed higher levels of GFRalpha 1 mRNA than GFRalpha 2 mRNA and neurons that were more sensitive to neurturin expressed higher levels of GFRalpha 2 mRNA than GFRalpha 1 mRNA . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| We here report that the glial cell line derived neurotrophic factor ( GDNF ) receptor GFRalpha 1 mRNA and GFRalpha 1 protein like immunoreactivity are upregulated in spinal motoneurons , and in dorsal root ganglion neurons of 30 month old 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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| First , immunohistochemical examination of the cerebral cortex of rats revealed that glial cell line derived neurotrophic factor receptor ( GFRalpha 1 ) was preferentially expressed on the cell membranes of capillary endothelial cells . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ 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 . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ Muscle contusion induced upregulation of GDNF and GFR alpha 1 mRNAs in Schwann cell like cells in the intramuscular nerves and of LIFR mRNA in damaged muscle cells . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Constitutive loss of Ret , its co receptor gfralpha 1 , or the ligand glial cell line derived neurotrophic factor results in renal agenesis . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| The changes in GFRalpha 1 and GFRalpha 2 expression after axotomy could be largely reversed by treatment with GDNF . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Tissue distributions of their respective receptors , GFR alpha 1 and GFR alpha 2 , reveal overlapping but distinct patterns of expression , which implies that the in vivo actions of GDNF and NTN may be different . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ Furthermore , introduction of these regions from GDNF , neurturin , or artemin into PSPN demonstrated that they are sufficient for activating GFRalpha 1 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| At early stages of development both the GDNF receptor , gfralpha 1 , and the neurturin ( NTN ) receptor , gfralpha 2 , were expressed in the oculomotor , facial and spinal accessory , and only gfralpha 1 in the trochlear , superior salivatory , trigeminal , hypoglossal and weakly in the dorsal motor nucleus of the vagus and the ambiguous nucleus . ^^^ A motor neuron subnuclei specific expression of gfralpha 1 and gfralpha 2 was seen in the facial and trigeminal nuclei which corresponded to their dependence on GDNF in null mutant mice . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| The localization of glial cell line derived neurotrophic factor ( GDNF ) family receptor alpha 1 ( GFRalpha 1 ) was investigated in rat brain by immunohistochemistry using a polyclonal antibody against a specific sequence of the rat protein . ^^^ As GFRalpha 1 protein was found in numerous brain structures , GDNF family ligands may have therapeutic application not only in degenerative diseases affecting in specific nervous systems , such as Parkinson ' s disease , amyotrophic lateral sclerosis and multiple system atrophy , but in diffusely damaging diseases like cerebrovascular diseases . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Whereas the GFRalpha 1 transcripts were detected at similar levels in normal tissues and in tumors , GDNF was frequently found expressed in sporadic tumors at levels several times higher than in controls . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Consequently , we found that RA alone induced the responsiveness of SCG neurons specifically to GDNF by upregulating the ligand specifying receptor for GDNF ( GFRalpha 1 ) at both the mRNA and protein levels . ^^^ On the other hand , BMP 2 , which had no significant effect by itself on the GDNF responsiveness , promoted the action of RA to upregulate GFRalpha 1 and enhance the GDNF responsiveness . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| GDNF signaling is mediated through a two component system consisting of the so called GDNF receptor alfa ( GFRalpha 1 ) which binds to GDNF . ^^^ 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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Following transaction of the sciatic nerve GDNF mRNA was up regulated rapidly in the denervated nerve distal to the cut along with the mRNA for one of its receptors , GFRalpha 1 . ^^^ GFRalpha 1 mRNA was also increased in the DRG ipsilateral to the nerve injury suggesting that GDNF may be involved in the trophic support of DRG sensory neurons . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| They bind to a specific membrane anchored GDNF family receptor as follows : GFRalpha 1 for GDNF , GFRalpha 2 for neurturin , GFRalpha 3 for enovin / artemin , and ( chicken ) GFRalpha 4 for persephin . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Broad specificity of GDNF family receptors GFRalpha 1 and GFRalpha 2 for GDNF and NTN in neurons and transfected cells . ^^^ The binding of soluble GFRalphas to transfected cells suggested that different GFRalphas were dedicated to particular ligands , with GDNF acting primarily or entirely through GFRalpha 1 , and neurturin ( NTN ) , through GFRalpha 2 . ^^^ By biochemical and genetic addition and / or deletion of GFRalpha 1 and 2 , we show that in both neuronal cell types , robust biological activities of GDNF or NTN can be mediated by either GFRalpha 1 or GFRalpha 2 , although GDNF is slightly more potent in dopaminergic ( DA ) neurons which normally express GFRalpha 1 , and NTN in submandibular neurons which normally express GFRalpha 2 . ^^^ Throughout the body , GDNF and NTN are likely to have important biological actions on both GFRalpha 1 and GFRalpha 2 expressing cells . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Thus , GFRalpha 1 , but not GFRalpha 2 , is absolutely required for the survival response of a majority of motoneurons to both GDNF and NTN . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Reactive astrocytes of the quinolinic acid lesioned rat striatum express GFRalpha 1 as well as GDNF in vivo . ^^^ Therefore , the present follow up experiment was performed with the aims : ( 1 ) to look at GDNF expression in the QA injected striatum at 28 days , ( 2 ) to look for possible immunohistochemical expression of GFRalpha 1 in the QA injected striatum at the same observation time , and ( 3 ) to use confocal microscopy of double immunofluorescence labeling of glial cell specific markers to identify the cell types expressing GDNF and GFRalpha 1 in the striatum at 28 days following a QA injection . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Expression of GFRalpha 1 , receptor for GDNF , in rat brain capillary during postnatal development of the BBB . ^^^ In the present study , we examined the relation between permeability of the BBB , using Evans blue as a tracer , and expression of the GDNF family receptor ( GFRalpha 1 ) during postnatal development of the BBB . ^^^ 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 . ^^^ The reciprocal relation between GFRalpha 1 expression and the permeability of the BBB strongly suggests active participation of GDNF in postnatal development of the BBB , although the mechanism ( s ) involved is still veiled . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| The timing of this shift corresponded to developmental changes in gut expression of GFR alpha 1 , a co receptor in the GDNF Ret signaling complex . ^^^ GFR alpha 1 could participate in GDNF signaling when expressed in cis on the surface of enteric precursor cells , or as a soluble protein . ^^^ The GDNF mediated response was greater when cell surface , compared with soluble , GFR alpha 1 was present , with the maximal response seen the presence of both cis and trans forms of GFR alpha 1 . ^^^ In addition to contributing to GDNF signaling , cell surface GFR alpha 1 modulated the specificity of interactions between GDNF and soluble GFR alphas . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Distinct hydrophobic and positively charged residues in this central region were required for binding of GFRalpha 1 to GDNF . ^^^ Interaction of GFRalpha 1 and GFRalpha 2 with GDNF and neurturin required distinct subsegments within this central domain , which allowed the construction of chimeric receptors that responded equally well to both ligands . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| The aim of the present study was to knockdown GDNF , its receptor GFR alpha 1 , and the related family member persephin by using antisense oligonucleotides and to observe the effects on cell proliferation . ^^^ This protocol markedly reduced GDNF and GFR alpha 1 protein levels in C 6 glioma cells compared with control oligonucleotides . ^^^ Knockdown of C 6 cells with GDNF and GFR alpha 1 but not with persephin antisense oligonucleotides significantly decreased the number of C 6 glioma cells and also inhibited the incorporation of bromodeoxyuridine as a sign of reduced DNA synthesis . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| In the present study , we immunohistochemically examined the expression of GDNF , neurturin ( NTN ) and their receptors , GFRalpha 1 for GDNF and GFRalpha 2 for NTN , because the capillaries of the inner BRB show specialization very similar to the blood brain barrier ( BBB ) . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Although both c Ret and GFRalpha 1 are required for responsiveness to GDNF , GFRalpha 1 is widely expressed in the absence of c Ret , suggesting alternative roles for `` ectopic ' ' sites of GFRalpha 1 expression . ^^^ These results provide an explanation for the tissue distribution of GFRalpha 1 , supporting the physiological importance of c Ret activation in trans as a novel mechanism to potentiate and diversify the biological responses to GDNF . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| We have identified zebrafish orthologues of glial cell line derived neurotrophic factor ( GDNF ) and the ligand binding component of its receptor GFRalpha 1 . ^^^ In the zebrafish PMN , GFRalpha 1 is only expressed in the CaP motor neuron while GDNF is expressed in the ventral somitic muscle that it innervates . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| GDNF and GFRalpha 1 are components of the axolotl pronephric duct guidance system . ^^^ 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 . ^^^ We provide evidence that GDNF signaling through GFRalpha 1 is sufficient to direct pathfinding of migrating pronephric duct cells in axolotl embryos by : ( 1 ) demonstrating that application of soluble GFRalpha 1 to an embryo lacking all GPI linked proteins rescues PND migration in a dose dependent fashion , ( 2 ) showing that application of excess soluble GFRalpha 1 to a normal embryo inhibits migration and that inhibition is dependent upon GDNF binding activity , and ( 3 ) showing that the PND will migrate toward a GDNF soaked bead in vivo , but will fail to migrate when GDNF is applied uniformly to the flank . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| GFRalpha 1 , GFRalpha 2 , GFRalpha 3 and GFRalpha 4 are the physiological coreceptors for GDNF , neurturin , artemin and persephin , respectively . ^^^ 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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| GDNF signals via GFRalpha 1 , neurturin via GFRalpha 2 , artemin via GFRalpha 3 , whereas the mammalian GFRalpha receptor for persephin ( PSPN ) is unknown . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Co stimulation with a soluble form of the GFRalpha 1 co receptor potentiated ligand dependent phosphorylation of different intracellular tyrosines to a similar extent and increased the survival of superior cervical ganglion neurons compared with treatment with GDNF alone . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Glial cell line derived neurotrophic factor ( GDNF ) and its receptors GFRalpha 1 and GFRalpha 2 in the human testis . ^^^ Glial cell line derived neurotrophic factor ( GDNF ) and its receptors GFRalpha 1 and GFRalpha 2 were found in the human testis during fetal development ( 15 34 weeks of gestation ) and in adult men ( 51 86 years of age ) by means of RT PCR , immunohistochemistry and Western blot techniques . ^^^ Glial cell line derived neurotrophic factor ( GDNF ) and its receptors GFRalpha 1 and GFRalpha 2 in the human testis . ^^^ Glial cell line derived neurotrophic factor ( GDNF ) and its receptors GFRalpha 1 and GFRalpha 2 were found in the human testis during fetal development ( 15 34 weeks of gestation ) and in adult men ( 51 86 years of age ) by means of RT PCR , immunohistochemistry and Western blot techniques . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 ) . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Presence of GDNF messenger ( m ) RNA and receptors GFRalpha 1 and GFRalpha 2 mRNA was analyzed by reverse transcription polymerase chain reaction . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| 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 ) . ^^^ 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 ) . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Genetic analysis of RET , GFR alpha 1 and GDNF genes in Spanish families with multiple endocrine neoplasia type 2A . ^^^ This locus encodes a receptor tyrosine kinase whose activation requires the formation of a multimeric receptor complex including GDNF as a ligand and GFR alpha 1 as a coreceptor . ^^^ 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 ) . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ In addition , these observations reveal that c Ret independent signaling of GFRalpha 1 is ligand specific and occurs only with GDNF . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| The mRNAs for receptors GFRalpha 1 and GFRalpha 2 were upregulated only after maximal GDNF upregulation and remained elevated as late as 6 months . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| RET ( Men2B ) transgene produces sympathoadrenal tumors but does not prevent intestinal aganglionosis in gdnf / or gfr alpha 1 ( / ) mice . ^^^ The ligand , GDNF , stimulates RET activity through a co receptor , GFR alpha 1 . ^^^ 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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| In the present study we localized glial cell line derived neurotrophic factor ( GDNF ) , and the high affinity receptor for GDNF ( GFRalpha 1 ) in the rat retina . ^^^ Our results also suggest that RGCs and retinal Mller cells may be responsive to GDNF because they both express GFRalpha 1 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Interestingly , we found that tyrosine hydroxylase ( TH ) positive neurons in the LC express both GFRalpha 1 and 2 receptors in a developmentally regulated fashion , suggesting a function for their preferred ligands : GDNF and NTN , respectively . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| We found that such neuroprotective effects are mediated through specific GDNF receptor alpha 1 ( GFRalpha 1 ) . ^^^ Animals with a deficiency in GFRalpha 1 have less GDNF induced neuroprotection . ^^^ These . data suggest that GDNF can protect against ischemic injury through a GFRalpha 1 / NOS mechanism . ^^^ We also found that the receptor for GDNF , GFRalpha 1 , and its signaling moiety c Ret were upregulated , starting immediately after ischemia . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Endogenous GDNF and its receptor , GFRalpha 1 , were detected in GMIR 1 cells by ELISA and immunohistochemistry / Western blot , respectively . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| The expression and localization of glial cell line derived neurotrophic factor ( GDNF ) and its receptor GFR alpha 1 in the testis were examined , because the blood testis barrier is a well known tissue barrier and we previously reported that GDNF reduced the endothelial permeability of the blood brain barrier ( BBB ) . ^^^ Because this relation between GDNF and GFR alpha 1 is similar to that observed in the BBB , we hypothesize that GDNF is a general regulator of tight junctions of the endothelium forming a blood tissue barrier in a paracrine fashion . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| GFRalpha 1 , a GPI anchored receptor for GDNF , is expressed as both membrane bound and secreted forms by accessory nerve cells and peripheral targets of developing sensory and sympathetic neurons during the period of target innervation . ^^^ 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 . ^^^ Soluble GFRalpha 1 prolongs GDNF mediated activation of cyclin dependent kinase 5 ( Cdk 5 ) , an event required for GFRalpha 1 induced neurite outgrowth and axon guidance . ^^^ Together with GDNF , target derived GFRalpha 1 can function in a non cell autonomous fashion as a chemoattractant cue with outgrowth promoting activity for peripheral neurons . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Ledda et al . , in this issue of Neuron , demonstrate that the target derived receptor glial cell line derived neurotrophic factor receptor alpha 1 ( GFRalpha 1 ) can also act in trans as an axon guidance molecule for neurons . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| We investigated the agonistic activities of N ( 4 ) ( 7 chloro 2 [ ( E ) 2 ( 2 chloro phenyl ) vinyl ] quinolin 4 yl ) N ( 1 ) , N ( 1 ) diethyl pentane 1 , 4 diamine ( XIB 4035 ) , at the glial cell line derived neurotrophic factor ( GDNF ) family receptoralpha 1 ( GFRalpha 1 ) in Neuro 2A cells , a mouse neuroblastoma cell line which is a suitable model for investigating functions mediated through GFRalpha 1 . ^^^ These results show that XIB 4035 may act as an agonist at GFRalpha 1 receptor complex , and mimic neurotrophic effects of GDNF in Neuro 2A cells . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| GDNF and NRTN bind to the tyrosine kinase receptor Ret and the receptors GFRalpha 1 and GFRalpha 2 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Here we demonstrated that during the course of postnatal development , nerve injury induced down regulation of the glial cell line derived neurotrophic factor ( GDNF ) receptor GFRalpha 1 in axotomized hypoglossal motoneurons of rat are gradually converted to the adult up regulation pattern of response . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| TGFbeta induces GDNF responsiveness in neurons by recruitment of GFRalpha 1 to the plasma membrane . ^^^ This is supported by the fact that GDNF in the presence of a soluble GFRalpha 1 can promote survival in the absence of TGFbeta . ^^^ Our data suggest that TGFbeta is involved in GFRalpha 1 membrane translocation , thereby permitting GDNF signaling and neurotrophic effects . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Differential expression of the cell line derived neurotrophic factor ( GDNF ) receptor GFRalpha 1 in heterozygous Gfralpha 1 null mutant mice after stroke . ^^^ 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 . ^^^ Since GDNF has neuroprotective effects , the reduced up regulation of Gfralpha 1 in Gfralpha 1 ( + / ) mice at early time points after ischemia suggests that the responsiveness to GDNF and GDNF receptor mediated neuroprotection is attenuated in these genetically modified animals and may underlie their greater vulnerability . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Glial cell derived neurothrophic factor ( GDNF ) interacts with a cell surface receptor , GFRalpha 1 , that is linked via a glycosyl phosphatidylinositol ( GPI ) lipid to the cell membrane . ^^^ 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 . ^^^ 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 . ^^^ Primary hippocampal neurons from transgenic mice that express a wild type GFRalpha 1 together with a mutant , tyrosine kinase inactive Ret also internalized GDNF efficiently ( approximately 20 % of total surface bound ligand internalized after 2 min ) . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| We also show that heparin at low concentrations protects GDNF from proteolytic modification by an endoprotease and also promotes the binding of GDNF to its receptor polypeptide , GFRalpha 1 . ^^^ The binding of human glial cell line derived neurotrophic factor to heparin and heparan sulfate : importance of 2 O sulfate groups and effect on its interaction with its receptor , GFRalpha 1 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Therefore , we examined the regulation of GDNF and its receptor ( GFR alpha 1 ) in colonic inflammation and its effects on colonic epithelial cell apoptosis . ^^^ METHODS : The expression of GDNF and GFR alpha 1 was investigated in experimental colitis of rats and in human inflammatory bowel disease ( IBD ) . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| We show that GFRalpha 1 , a component of GDNF receptor , was expressed in thymocytes at an early stage of thymocyte development and was involved in the survival of thymocyte precursors . ^^^ Possible involvement of glial cell line derived neurotrophic factor and its receptor , GFRalpha 1 , in survival and maturation of thymocytes . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Interestingly , both lipopolysaccharide and TNFalpha triggered a significant decrease in the expression of the GDNF receptor , GFRalpha 1 , in glial cells . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Identification of a surface for binding to the GDNF GFR alpha 1 complex in the first cadherin like domain of RET . ^^^ Cross linking experiments have indicated that the RETECD makes direct contacts with both the GDNF ligand and GFR alpha 1 molecule in the complex , although it has low or no detectable affinity for either component alone . ^^^ 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 . ^^^ We found that Xenopus RETECD was unable to bind to GDNF GFR alpha 1 or neurturin ( NTN ) GFR alpha 2 complexes of mammalian origin . ^^^ Subsequent loss of function experiments at higher resolution identified three small subsets of residues , mapping on the same face of the molecular model of RET CLD 1 , that were required for the interaction of human RETECD with the GDNF GFR alpha 1 complex . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| CONCLUSIONS : In the course of recovery spermatogenesis , the expression of GFR alpha 1 plays a key role in turning the spermatogonial stem cell reactivity to GDNF , which promotes self renewal at a high level , or results in differentiation at a low level . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 ) . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ GFRalpha 1 has a putative domain structure of three homologous cysteine rich domains , where domains 2 and 3 make up a central domain responsible for GDNF binding . ^^^ The structure was used to model the homologous domain 2 , the other half of the GDNF binding fragment , and to construct the first structural model of the GDNF GFRalpha 1 interaction . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ Optic nerve transection resulted in reduced Ret mRNA levels in retina , while the levels of GDNF , GFRalpha 1 , and 2 mRNA increased . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| It has been unknown whether the GDNF receptor , GFRalpha 1 , may play a role in regulating either phase . ^^^ Glial cell line derived neurotrophic factor receptor GFRalpha 1 is expressed in the rat striatum during postnatal development . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ 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 . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ 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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Analysis of the expression of the glial cell line derived neurotrophic factor ( GDNF ) and its receptors GFRalpha 1 , GFRalpha 2 , and GFRalpha 3 using triple immunofluorescence and confocal laser scanning microscopy revealed that in all animals showing marked hippocampal DND , the neuronal staining for GFRalpha 1 , GFRalpha 3 , and GDNF decreased prior to the onset of TUNEL staining in CA 1 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ We established cell lines expressing either GFRalpha 1 isoforms and demonstrated that the GFRalpha1b isoform binds GDNF more efficiently than GFRalpha1a . ^^^ 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 . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Studies on protein phosphorylation and specific inhibitors of cell signal transduction indicate that GDNF function is mediated by receptor GFRalpha 1 and involves MAPK , cAMP / cAMP responsive element binding factor and Src kinase activities . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Expression of GDNF and GFR alpha 1 in mouse taste bud cells . ^^^ Using an immunocytochemical method , we examined whether the taste bud cells in the circumvallate papillae of normal mice expressed GDNF and its GFR alpha 1 receptor . ^^^ Using double immunostaining for either of them and NCAM , PGP 9 . 5 , or alpha gustducin , we additionally sought to determine what type of taste bud cells expressed GDNF or GFR alpha 1 , because NCAM is reported to be expressed in type 3 cells , PGP 9 . 5 , in type 3 and some type 2 cells , and alpha gustducin , in some type 2 cells . ^^^ Normal taste bud cells expressed both GDNF and GFR alpha 1 . ^^^ The percentage of GDNF immunoreactive cells among all taste bud cells was 31 . 63 % , and that of GFR alpha 1 immunoreactive cells , 83 . 21 % . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| GDNF enhanced the phagocytic activity of the macrophages via GFRalpha 1 , glycosylphosphatidylinositol anchored specific binding site of GDNF , in a c Ret independent manner . ^^^ However , the GDNF mRNA level , but not the MCP 1 or GFRalpha 1 mRNA level , was substantially lower in the mutant macrophages than in the + / + cells irrespective of stimulation with MCP 1 or lipopolysaccharide ( LPS ) . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Moreover , the cells expressed detectable levels of protein markers specific for germ cells such as Dazl , and specific for germ line stem cells such as Oct 4 , a transcription factor , and GFRalpha 1 , the receptor for glial cell line derived neurotrophic factor ( GDNF ) . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| We show in the present study that GFR alpha 1 , the receptor for GDNF ( glial cell line derived neurotrophic factor ) , is strongly expressed by a subset of type A spermatogonia in the basal part of the seminiferous epithelium . ^^^ The isolated cells express Ret , a tyrosine kinase transmembrane receptor that mediates the intracellular response to GDNF via GFR alpha 1 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Glial cell line derived neurotrophic factor ( GDNF ) receptor alpha 1 ( GFR alpha 1 ) is highly selective for GDNF versus artemin . ^^^ To clarify whether glial cell line derived neurotrophic factor ( GDNF ) receptor alpha 1 ( GFRalpha 1 ) , the glycosylphosphatidylinositol ( GPI ) linked coreceptor for GDNF , is also a functional coreceptor for artemin ( ART ) , we have studied receptor binding , signaling , and neuronal survival . ^^^ 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 . ^^^ However , using GFRalpha 1 transfected NB41A3 cells , ART showed no detectable competition against the binding of ( 125 ) 1 labeled GDNF . ^^^ When rat primary dorsal root ganglion ( DRG ) neurons were used , only the survival promoting activity of GDNF and not that of ART was blocked by an anti GFRalpha 1 antibody . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| GDNF and GFRalpha 1 promote differentiation and tangential migration of cortical GABAergic neurons . ^^^ GDNF signaling via GFRalpha 1 was found to promote the differentiation of ventral precursors into GABAergic cells , enhancing their neuronal morphology and motility . ^^^ 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 . ^^^ We conclude that one of the normal functions of GDNF signaling via GFRalpha 1 in the developing brain is to promote the differentiation and migration of cortical GABAergic neurons . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Unlike hRET , however , the extracellular domain of dRET was unable to interact with mammalian GDNF and GFRalpha 1 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Using immunomagnetic cell sorting , testis cells were selected for the expression of alpha ( 6 ) integrin , alpha ( 5 ) integrin , c kit receptor tyrosine kinase ( Kit ) , or a binding subunit of glial cell line derived neurotrophic factor ( GDNF ) receptor , GFRalpha 1 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 ) . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ To further understand GDNF and its receptor system in the PNS , we first characterized the expression of GFRalpha 1 in bovine peripheral nerve in vivo . ^^^ 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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| We confirmed that GDNF , GFRalpha 1 and NCAM are expressed in neonatal rat SCs . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| In branching UBs induced by whole metanephric mesenchyme cell conditioned medium , proliferating cells were localized at ampullae , where a binding receptor for GDNF , GFRalpha 1 , was found . ^^^ For example , the mRNA for the GDNF receptors , GFRalpha 1 and ret 9 , was down regulated , whereas the mRNA for collecting duct transporters , such as urea transporter 2 , aquaporin 3 , and sodium hydrogen exchanger 2 was up regulated in HRG treated UBs compared with UBs grown in the presence of branch promoting factors . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Glial cell line derived neurotrophic factor ( GDNF ) exerts its effect through a multi component receptor system consisting of GFRalpha 1 , RET and NCAM . ^^^ Glial cell line derived neurotrophic factor ( GDNF ) exerts its effect through a multi component receptor system consisting of GFRalpha 1 , RET and NCAM . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| In the mouse , spermatogonial stem cells express GFRalpha 1 , the receptor for GDNF , and respond to this growth factor in vivo and in vitro . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ These findings indicate that GDNF mediates trophic effects on the survival and target innervation of the periodontal Ruffini endings via GFRalpha 1 and RET . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| In addition , MSCs express a variety of growth factor receptors including the glycosyl phosphatidylinositol anchored ligand binding subunit of the GDNF receptor , GFRalpha 1 , as well as fibroblast growth factor receptors one and four . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| The present study examined the expression of GDNF and GFRalpha 1 ( the high affinity receptor of GDNF ) in dorsal root ganglions ( DRG ) in a rat model of neuropathic pain induced by chronic constriction injury ( CCI ) to the sciatic nerve . ^^^ In order to address the role of GDNF and GFRalpha 1 in neuropathic pain , antisense oligodeoxynucleotide ( ODN ) specifically against GFRalpha 1 was intrathecally administered to result in down regulation of GFRalpha 1 expression . ^^^ The results showed that both the protein and mRNA levels of GDNF and GFRalpha 1 were significantly increased after CCI , while the thermal hyperalgesia of neuropathic pain rats could be significantly aggravated by antisense ODN treatment , but not by normal saline ( NS ) or mismatch ODN treatment . ^^^ The present study demonstrated that endogenous GDNF and GFRalpha 1 might play an anti hyperalgesic role in neuropathic pain of rats . ^^^ In addition , we found a down regulation of somatostatin ( SOM ) in DRG and spinal dorsal horn after expression of GFRalpha 1 was knocked down , which suggested the possible relationship between the anti hyperalgesic effect of GDNF and GFRalpha 1 on neuropathic pain and endogenous SOM . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Here , we show that glial cell line derived neurotrophic factor ( GDNF ) is produced in the olfactory bulb but distributed along the rostral migratory stream ( RMS ) in a pattern concordant with the expression of its GPI anchored receptor GFRalpha 1 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| The present study was undertaken to determine whether the GDNF receptor , GFRalpha 1 , is expressed by pulpal afferents , and , further , to determine whether tooth injury evokes changes in expression of the GDNF and NGF receptors among pulpal afferents . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Neurturin and glial cell line derived neurotrophic factor ( GDNF ) are neurotrophic factors for penile parasympathetic neurons , so we also examined expression of relevant receptors , GFRalpha 1 and GFRalpha 2 , in injured pelvic ganglion neurons . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| The GDNF receptor GFRalpha 1 was upregulated in the SVZ 1 week after MCAO and was coexpressed with markers of dividing progenitor cells . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| GDNF family ligand receptor components Ret and GFRalpha 1 in the human trigeminal ganglion and sensory nuclei . ^^^ The majority of Ret+ are double labeled for GFRalpha 1 and glial cell line derived neurotrophic factor ( GDNF ) . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Primer pairs specific for GDNF ( isoforms 1 and 2 ) , and its receptor molecules , GFRalpha 1 and cRET were utilized . ^^^ GDNF , cRET and GFRalpha 1 mRNA expression was clearly detected in the putamen of control and Parkinson ' s disease patients . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| The key role of GDNF and its receptor GFRalpha 1 in enteric nervous system development is conserved from zebrafish to humans . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| Glial cell line derived neurotrophic factor ( GDNF ) has two receptors , receptor tyrosine kinase c ret and glycosylphosphatidylinositol linked cell surface receptor GDNFRalpha . ^^^ 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 . ^^^ 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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| However , these cells did not express the mRNA for GDNFRalpha , the other component of the GDNF receptor complex . . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| The DNA sequences of 5 further genes ( GDNF , GDNFRalpha , EDN 3 , EDNRB , and NTN ) , that may contribute to the development of HSCR , have not shown mutations in the patients analyzed so far . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ Glial cell line derived neurotrophic factor ( Gdnf ) and its alpha receptor ( Gfra 1 ) interact with the Ret receptor triggering its tyrosine kinase activity . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P56159 and P39905 |
Pubmed |
SVM Score :0.0 |
| NA |
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