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- W2099696075 abstract "Previous studies from our laboratory have shown that epidermal growth factor (EGF) stimulates cAMP accumulation in the heart via a process involving Gsα and the EGF receptor (EGFR) protein tyrosine kinase activity (Nair, B. G., Parikh, B., Milligan, G., and Patel, T. B.(1990) J. Biol. Chem. 265, 21317-21322; Nair, B. G., and Patel, T. B.(1993) Biochem. Pharmacol. 46, 1239-1245). Therefore, studies were performed to investigate the hypothesis that the EGFR protein tyrosine kinase phosphorylates Gsα and activates this protein. Employing purified EGFR and Gsα, we have demonstrated that the EGFR kinase phosphorylates Gsα in a time-dependent manner with a stoichiometry of 2 mol of phosphate incorporated/mol of Gsα. As determined by phosphoamino acid analysis, the phosphorylation of Gsα by the EGFR kinase was exclusively on tyrosine residues. Interestingly, GDP and guanosine 5′-3-O-(thio)triphosphate (GTPγS) inhibited the phosphorylation of Gsα without altering EGFR autophosphorylation. However, G protein βγ subunits protected against GDP- and GTPγS-mediated inhibition of phosphorylation of GSα. In functional studies, phospho-Gsα demonstrated a greater GTPase activity and also a greater capacity to bind GTPγS as compared to the nonphosphorylated Gsα. Moreover, the phospho-Gsα augmented adenylyl cyclase activity in S49 cyc- cell membranes to a greater extent than its nonphosphorylated counterpart. Therefore, we conclude that phosphorylation of Gsα on tyrosine residues by the EGFR kinase activates this G protein and increases its ability to stimulate adenylyl cyclase. Previous studies from our laboratory have shown that epidermal growth factor (EGF) stimulates cAMP accumulation in the heart via a process involving Gsα and the EGF receptor (EGFR) protein tyrosine kinase activity (Nair, B. G., Parikh, B., Milligan, G., and Patel, T. B.(1990) J. Biol. Chem. 265, 21317-21322; Nair, B. G., and Patel, T. B.(1993) Biochem. Pharmacol. 46, 1239-1245). Therefore, studies were performed to investigate the hypothesis that the EGFR protein tyrosine kinase phosphorylates Gsα and activates this protein. Employing purified EGFR and Gsα, we have demonstrated that the EGFR kinase phosphorylates Gsα in a time-dependent manner with a stoichiometry of 2 mol of phosphate incorporated/mol of Gsα. As determined by phosphoamino acid analysis, the phosphorylation of Gsα by the EGFR kinase was exclusively on tyrosine residues. Interestingly, GDP and guanosine 5′-3-O-(thio)triphosphate (GTPγS) inhibited the phosphorylation of Gsα without altering EGFR autophosphorylation. However, G protein βγ subunits protected against GDP- and GTPγS-mediated inhibition of phosphorylation of GSα. In functional studies, phospho-Gsα demonstrated a greater GTPase activity and also a greater capacity to bind GTPγS as compared to the nonphosphorylated Gsα. Moreover, the phospho-Gsα augmented adenylyl cyclase activity in S49 cyc- cell membranes to a greater extent than its nonphosphorylated counterpart. Therefore, we conclude that phosphorylation of Gsα on tyrosine residues by the EGFR kinase activates this G protein and increases its ability to stimulate adenylyl cyclase." @default.
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- W2099696075 date "1996-03-01" @default.
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- W2099696075 title "Activation of Gsα by the Epidermal Growth Factor Receptor Involves Phosphorylation" @default.
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- W2099696075 doi "https://doi.org/10.1074/jbc.271.12.6947" @default.
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