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

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Abstract
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.

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