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Stimulation of the α 1A adrenergic receptor inhibits PDGF‐induced PDGF β receptor Tyr751 phosphorylation and PI 3‐kinase activation
Author(s) -
Lin Hong-Ying,
Ballou Lisa M,
Lin Richard Z
Publication year - 2003
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(03)00233-3
Subject(s) - platelet derived growth factor receptor , tyrosine kinase , receptor tyrosine kinase , tyrosine phosphorylation , chemistry , biology , phosphorylation , microbiology and biotechnology , receptor , signal transduction , biochemistry , growth factor
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.