GDNF triggers a novel Ret‐independent Src kinase family‐coupled signaling via a GPI‐linked GDNF receptor α1

FEBS Letters

Sun, Yun Fu²  Arumäe, Urmas²  Lindahl, Maria²  Saarma, Mart²  Titievsky, Alexey²  Thomas-Crusells, Judith²  Billaud, Marc¹  Poteryaev, Dmitry² 

[1] Laboratoire de Génétique, Université Claude Bernard, Lyon, France;Institute of Biotechnology, Program for Molecular Neurobiology, Viikki Biocenter, P.O. Box 56, FIN-00014 University of Helsinki, Finland

关键词: Glial cell line-derived neurotrophic factor;    Glycosyl-phosphatidylinositol-linked receptor;    Ret tyrosine kinase;    Src family kinase;    Mitogen-activated protein kinase;    cAMP response element binding protein;    GDNF;    glial cell line-derived neurotrophic factor;    GFRα1;    GDNF receptor α1;    DRG;    dorsal root ganglion;    MAPK;    mitogen-activated protein kinase;    CREB;    cAMP response element binding protein;   

DOI  :  10.1016/S0014-5793(99)01590-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown