Characterization of a multicomponent receptor for GDNF
| Autor: | Mark W. Moore, Donna M. Stone, Mark Armanini, Franz Hefti, James J.S. Treanor, Alun M. Davies, Richard A. Pollock, Laurie J. Goodman, Christopher E. Henderson, Masahide Takahashi, Arnon Rosenthal, Kristian Todd Poulsen, Naoya Asai, Christa L. Gray, Heidi S. Phillips, Richard Vandlen, Frederic J. de Sauvage, Audry Goddard, Claus D. Beck, Anna Buj-Bello |
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| Přispěvatelé: | Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon |
| Rok vydání: | 1996 |
| Předmět: |
0303 health sciences
Multidisciplinary biology urogenital system animal diseases Neurturin Persephin Artemin [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Tyrosine phosphorylation Molecular biology Cell biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine nervous system chemistry Proto-Oncogene Proteins c-ret Neurotrophic factors Glial cell line-derived neurotrophic factor biology.protein GDNF family of ligands ComputingMilieux_MISCELLANEOUS 030217 neurology & neurosurgery 030304 developmental biology |
| Zdroj: | ResearcherID Nature Nature, 1996, 382 (6586), pp.80-83. ⟨10.1038/382080A0⟩ Nature, Nature Publishing Group, 1996, 382 (6586), pp.80-83. ⟨10.1038/382080A0⟩ |
| ISSN: | 1476-4687 0028-0836 1476-4679 |
| Popis: | Glial-cell-line-derived neurotrophic factor (GDNF) is a potent survival factor for central and peripheral neurons, and is essential for the development of kidneys and the enteric nervous system. Despite the potential clinical and physiological importance of GDNF, its mechanism of action is unknown. 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. |
| Databáze: | OpenAIRE |
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