GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF - PubMed (original) (raw)

. 1996 Jun 28;85(7):1113-24.

doi: 10.1016/s0092-8674(00)81311-2.

D Wen, Y Yu, P L Holst, Y Luo, M Fang, R Tamir, L Antonio, Z Hu, R Cupples, J C Louis, S Hu, B W Altrock, G M Fox

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• PMID: 8674117
• DOI: 10.1016/s0092-8674(00)81311-2

Free article

GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF

S Jing et al. Cell. 1996.

Free article

Abstract

We report the expression cloning and characterization of GDNFR-alpha, a novel glycosylphosphatidylinositol-linked cell surface receptor for glial cell line-derived neurotrophic factor (GDNF). GDNFR-alpha binds GDNF specifically and mediates activation of the Ret protein-tyrosine kinase (PTK). Treatment of Neuro-2a cells expressing GDNFR-alpha with GDNF rapidly stimulates Ret autophosphorylation. Ret is also activated by treatment with a combination of GDNF and soluble GDNFR-alpha in cells lacking GDNFR-alpha, and this effect is blocked by a soluble Ret-Fc fusion protein. Ret activation by GDNF was also observed in cultured embryonic rat spinal cord motor neurons, a cell type that responds to GDNF in vivo. A model for the stepwise formation of a GDNF signal-transducing complex including GDNF, GDNFR-alpha, and the Ret PTK is proposed.

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