Stimulation of the alpha1A adrenergic receptor inhibits PDGF-induced PDGF beta receptor Tyr751 phosphorylation and PI 3-kinase activation.
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Stimulation of the alpha1A adrenergic receptor inhibits PDGF-induced PDGF beta receptor Tyr751 phosphorylation and PI 3-kinase activation. / Lin, Hongying; Ballou, Lisa M; Lin, Richard Z.
in: FEBS LETT, Jahrgang 540, Nr. 1-3, 1-3, 2003, S. 106-110.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Stimulation of the alpha1A adrenergic receptor inhibits PDGF-induced PDGF beta receptor Tyr751 phosphorylation and PI 3-kinase activation.
AU - Lin, Hongying
AU - Ballou, Lisa M
AU - Lin, Richard Z
PY - 2003
Y1 - 2003
N2 - Several reports indicate that some G(alphaq)-coupled receptors antagonize the activation of phosphatidylinositol (PI) 3-kinase by receptor tyrosine kinases. We used Rat-1 fibroblasts expressing the alpha(1A) adrenergic receptor to study how this G(alphaq)-coupled receptor inhibits platelet-derived growth factor (PDGF) activation of PI 3-kinase. Phenylephrine (PE) stimulation of the alpha(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 C gamma 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(alphaq). These results suggest that the alpha(1A) adrenergic receptor, and perhaps other G(alphaq)-coupled receptors, uses tyrosine dephosphorylation to block PI 3-kinase activation by PDGF.
AB - Several reports indicate that some G(alphaq)-coupled receptors antagonize the activation of phosphatidylinositol (PI) 3-kinase by receptor tyrosine kinases. We used Rat-1 fibroblasts expressing the alpha(1A) adrenergic receptor to study how this G(alphaq)-coupled receptor inhibits platelet-derived growth factor (PDGF) activation of PI 3-kinase. Phenylephrine (PE) stimulation of the alpha(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 C gamma 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(alphaq). These results suggest that the alpha(1A) adrenergic receptor, and perhaps other G(alphaq)-coupled receptors, uses tyrosine dephosphorylation to block PI 3-kinase activation by PDGF.
M3 - SCORING: Zeitschriftenaufsatz
VL - 540
SP - 106
EP - 110
JO - FEBS LETT
JF - FEBS LETT
SN - 0014-5793
IS - 1-3
M1 - 1-3
ER -
