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Publication : Characterization of a multicomponent receptor for GDNF.

First Author  Treanor JJ Year  1996
Journal  Nature Volume  382
Issue  6586 Pages  80-3
PubMed ID  8657309 Mgi Jnum  J:33824
Mgi Id  MGI:81317 Doi  10.1038/382080a0
Citation  Treanor JJ, et al. (1996) Characterization of a multicomponent receptor for GDNF [see comments]. Nature 382(6586):80-3
abstractText  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.
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