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.
Mesh Terms:
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
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
Cell
Date: Jun. 28, 1996
PubMed ID: 8674117
View in: Pubmed Google Scholar
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