Characterization of a multicomponent receptor for GDNF

J. J.S. Treanor, L. Goodman, F. De Sauvage, D. M. Stone, K. T. Poulsen, C. D. Beck, C. Gray, M. P. Armanini, R. A. Pollock, F. Hefti, H. S. Phillips, A. Goddard, M. W. Moore, A. Buj-Bello, A. M. Davies, N. Asai, M. Takahashi, R. Vandien, C. E. Henderson, A. Rosenthal

Research output: Contribution to journalArticlepeer-review

935 Citations (Scopus)

Abstract

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-α) that is expressed on GDNF-responsive ceils and binds GDNF with a high affinity. We further demonstrate that GDNF promotes the formation of a physical complex between GDNFR-α and the orphan tyrosine kinase receptor Ret, thereby inducing its tyrosine phosphorylation. These findings support the hypothesis that GDNF uses a multi-subunit receptor system in which GDNFR-α and Ret function as the ligand-binding and signalling components, respectively.

Original languageEnglish
Pages (from-to)80-83
Number of pages4
JournalNature
Volume382
Issue number6586
DOIs
Publication statusPublished - 02-08-1996
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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