[HTML][HTML] GDNF–induced activation of the ret protein tyrosine kinase is mediated by GDNFR-α, a novel receptor for GDNF
S Jing, D Wen, Y Yu, PL Holst, Y Luo, M Fang, R Tamir… - Cell, 1996 - cell.com
S Jing, D Wen, Y Yu, PL Holst, Y Luo, M Fang, R Tamir, L Antonio, Z Hu, R Cupples…
Cell, 1996•cell.comWe report the expression cloning and characterization of GDNFR-α, a novel
glycosylphosphatidylinositol-linked cell surface receptor for glial cell line–derived
neurotrophic factor (GDNF). GDNFR-α binds GDNF specifically and mediates activation of
the Ret protein-tyrosine kinase (PTK). Treatment of Neuro-2a cells expressing GDNFR-α
with GDNF rapidly stimulates Ret autophosphorylation. Ret is also activated by treatment
with a combination of GDNF and soluble GDNFR-α in cells lacking GDNFR-α, and this effect …
glycosylphosphatidylinositol-linked cell surface receptor for glial cell line–derived
neurotrophic factor (GDNF). GDNFR-α binds GDNF specifically and mediates activation of
the Ret protein-tyrosine kinase (PTK). Treatment of Neuro-2a cells expressing GDNFR-α
with GDNF rapidly stimulates Ret autophosphorylation. Ret is also activated by treatment
with a combination of GDNF and soluble GDNFR-α in cells lacking GDNFR-α, and this effect …
Abstract
We report the expression cloning and characterization of GDNFR-α, a novel glycosylphosphatidylinositol-linked cell surface receptor for glial cell line–derived neurotrophic factor (GDNF). GDNFR-α binds GDNF specifically and mediates activation of the Ret protein-tyrosine kinase (PTK). Treatment of Neuro-2a cells expressing GDNFR-α with GDNF rapidly stimulates Ret autophosphorylation. Ret is also activated by treatment with a combination of GDNF and soluble GDNFR-α in cells lacking GDNFR-α, 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-α, and the Ret PTK is proposed.
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