GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF.
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.
Pubmed ID: 8674117 RIS Download
Amino Acid Sequence | Animals | Base Sequence | Cells, Cultured | Cloning, Molecular | Dose-Response Relationship, Drug | Drosophila Proteins | Fetus | Glial Cell Line-Derived Neurotrophic Factor | Glial Cell Line-Derived Neurotrophic Factor Receptors | Glycosylphosphatidylinositols | Membrane Proteins | Mice | Mice, Inbred C57BL | Molecular Sequence Data | Motor Neurons | Nerve Growth Factors | Nerve Tissue Proteins | Phosphorylation | Proto-Oncogene Proteins | Proto-Oncogene Proteins c-ret | Rats | Rats, Sprague-Dawley | Receptor Protein-Tyrosine Kinases | Receptors, Nerve Growth Factor | Recombinant Proteins | Retina | Spinal Cord | Tyrosine