Insulin antagonizes ischemia-induced Thr172 phosphorylation of AMP-activated protein kinase alpha-subunits in heart via hierarchical phosphorylation of Ser485/491.

Abstract : Previous studies showed that insulin antagonizes AMP-activated protein kinase activation by ischemia and that protein kinase B might be implicated. Here we investigated whether the direct phosphorylation of AMP-activated protein kinase by protein kinase B might participate in this effect. Protein kinase B phosphorylated recombinant bacterially expressed AMP-activated protein kinase heterotrimers at Ser(485) of the alpha1-subunits. In perfused rat hearts, phosphorylation of the alpha1/alpha2 AMP-activated protein kinase subunits on Ser(485)/Ser(491) was increased by insulin and insulin pretreatment decreased the phosphorylation of the alpha-subunits at Thr(172) in a subsequent ischemic episode. It is proposed that the effect of insulin to antagonize AMP-activated protein kinase activation involves a hierarchical mechanism whereby Ser(485)/Ser(491) phosphorylation by protein kinase B reduces subsequent phosphorylation of Thr(172) by LKB1 and the resulting activation of AMP-activated protein kinase.
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Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2006, 281 (9), pp.5335-40. 〈10.1074/jbc.M506850200〉
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Soumis le : mardi 2 juin 2009 - 23:29:42
Dernière modification le : mardi 7 juillet 2009 - 11:32:09

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Sandrine Horman, Didier Vertommen, Richard Heath, Dietbert Neumann, Véronique Mouton, et al.. Insulin antagonizes ischemia-induced Thr172 phosphorylation of AMP-activated protein kinase alpha-subunits in heart via hierarchical phosphorylation of Ser485/491.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2006, 281 (9), pp.5335-40. 〈10.1074/jbc.M506850200〉. 〈inserm-00390879〉

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