期刊
FEBS LETTERS
卷 540, 期 1-3, 页码 106-110出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-5793(03)00233-3
关键词
phosphatidylinositol 3-kinase; G(q)-coupled receptor; Akt; SHP-2; Pasteurella multocida toxin
资金
- NIDDK NIH HHS [R01 DK62722] Funding Source: Medline
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 Of 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(aq)-coupled receptors, uses tyrosine dephosphorylation to block PI 3-kinase activation by PDGF. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
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