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. 2006 Mar 3;281(9):5335-40.
doi: 10.1074/jbc.M506850200. Epub 2005 Dec 9.

Insulin Antagonizes Ischemia-Induced Thr172 Phosphorylation of AMP-activated Protein Kinase Alpha-Subunits in Heart via Hierarchical Phosphorylation of Ser485/491

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Insulin Antagonizes Ischemia-Induced Thr172 Phosphorylation of AMP-activated Protein Kinase Alpha-Subunits in Heart via Hierarchical Phosphorylation of Ser485/491

Sandrine Horman et al. J Biol Chem. .
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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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