GDNF triggers a novel Ret‐independent Src kinase family‐coupled signaling via a GPI‐linked GDNF receptor α1
Copyright policy )GDNF triggers a novel Ret‐independent Src kinase family‐coupled signaling via a GPI‐linked GDNF receptor α1
Glial cell line‐derived neurotrophic factor (GDNF) has potentially great clinical importance in the treatment of Parkinson's disease and several other neurodegenerative diseases, however its intracellular signaling mechanisms are poorly understood. Here we show that upon GDNF binding glycosyl‐phosphatidylinositol (GPI)‐linked GDNF receptor α1 (GFRα1) activates cytoplasmic Src family tyrosine kinase(s) in Ret tyrosine kinase‐deficient cultured mouse dorsal root ganglion neurons and in two Ret‐negative cell lines. GFRα1‐mediated Src‐type kinase activation subsequently triggers phosphorylation of mitogen‐activated protein kinase, cAMP response element binding protein and phospholipase Cγ. We therefore conclude that GDNF can activate intracellular signaling pathways Ret‐independently via GPI‐linked GFRα1.
- Claude Bernard University Lyon 1 France
- University of Helsinki Finland
- Claude Bernard University Lyon 1 France
Glycosyl-phosphatidylinositol-linked receptor, Glial Cell Line-Derived Neurotrophic Factor Receptors, Ret tyrosine kinase, MAP Kinase Signaling System, Nerve Tissue Proteins, Glial cell line-derived neurotrophic factor, cAMP response element binding protein, Mice, Ganglia, Spinal, Proto-Oncogene Proteins, Animals, Drosophila Proteins, Humans, Glial Cell Line-Derived Neurotrophic Factor, Nerve Growth Factors, Phosphorylation, Cyclic AMP Response Element-Binding Protein, Cells, Cultured, Phospholipase C gamma, Proto-Oncogene Proteins c-ret, 3T3 Cells, Mitogen-activated protein kinase, Src family kinase, Enzyme Activation, Isoenzymes, Mitogen-Activated Protein Kinases
Glycosyl-phosphatidylinositol-linked receptor, Glial Cell Line-Derived Neurotrophic Factor Receptors, Ret tyrosine kinase, MAP Kinase Signaling System, Nerve Tissue Proteins, Glial cell line-derived neurotrophic factor, cAMP response element binding protein, Mice, Ganglia, Spinal, Proto-Oncogene Proteins, Animals, Drosophila Proteins, Humans, Glial Cell Line-Derived Neurotrophic Factor, Nerve Growth Factors, Phosphorylation, Cyclic AMP Response Element-Binding Protein, Cells, Cultured, Phospholipase C gamma, Proto-Oncogene Proteins c-ret, 3T3 Cells, Mitogen-activated protein kinase, Src family kinase, Enzyme Activation, Isoenzymes, Mitogen-Activated Protein Kinases
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