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GDNF triggers a novel Ret‐independent Src kinase family‐coupled signaling via a GPI‐linked GDNF receptor α1
Author(s) -
Poteryaev Dmitry,
Titievsky Alexey,
Sun Yun Fu,
Thomas-Crusells Judith,
Lindahl Maria,
Billaud Marc,
Arumäe Urmas,
Saarma Mart
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01590-2
Subject(s) - gdnf family of ligands , glial cell line derived neurotrophic factor , microbiology and biotechnology , proto oncogene proteins c ret , proto oncogene tyrosine protein kinase src , src family kinase , tyrosine kinase , biology , receptor tyrosine kinase , signal transduction , neurotrophic factors , chemistry , cancer research , biochemistry , receptor
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.