Stimulation of the α1A adrenergic receptor inhibits PDGF‐induced PDGF β receptor Tyr751 phosphorylation and PI 3‐kinase activation

FEBS Letters

Lin, Richard Z²  Ballou, Lisa M²  Lin, Hong-Ying¹ 

[1] Institute of Genetics, Roemerstr. 164, University of Bonn, 53117 Bonn, Germany;Department of Medicine, Division of Hematology, Stony Brook University, Stony Brook, NY 11794-8151, USA

关键词: Phosphatidylinositol 3-kinase;    Gq-coupled receptor;    Akt;    SHP-2;    Pasteurella multocida toxin;    PI;    phosphatidylinositol;    PDGF;    platelet-derived growth factor;    PDGFR;    PDGF receptor;    PE;    phenylephrine;    PLC;    phospholipase C;    PMT;    Pasteurella multocida toxin;    SH;    Src homology;    IGF-I;    insulin-like growth factor I;    IRS-1;    insulin receptor substrate-1;   

DOI  :  10.1016/S0014-5793(03)00233-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Several reports indicate that some G_αq-coupled receptors antagonize the activation of phosphatidylinositol (PI) 3-kinase by receptor tyrosine kinases. We used Rat-1 fibroblasts expressing the α_1A adrenergic receptor to study how this G_αq-coupled receptor inhibits platelet-derived growth factor (PDGF) activation of PI 3-kinase. Phenylephrine (PE) stimulation of the α_1A adrenergic receptor inhibited PDGF-induced binding of PI 3-kinase to the PDGF receptor (PDGFR) and phosphorylation of the PDGFR at Tyr751, which forms a docking site for PI 3-kinase. By contrast, activation of phospholipase Cγ by PDGF and phosphorylation of the PDGFR at Tyr716 and Tyr771 were not inhibited by PE. The protein tyrosine phosphatase SHP-2, which dephosphorylates Tyr751 on the PDGFR, was more active in cells treated with PDGF plus PE than in cells treated with either agent alone. PDGF-induced PI 3-kinase signaling was also inhibited by treatment of cells with Pasteurella multocida toxin to activate G_αq. These results suggest that the α_1A adrenergic receptor, and perhaps other G_αq-coupled receptors, uses tyrosine dephosphorylation to block PI 3-kinase activation by PDGF.

【 授权许可】

Unknown