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J Biol Chem. 2006 Mar 3;281(9):5335-40. 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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1
Hormone and Metabolic Research Unit, Christian de Duve Institute of Cellular Pathology and Université catholique de Louvain, Avenue Hippocrate 75, B-1200 Brussels, Belgium. sandrine.horman@horm.ucl.ac.be

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.

PMID:
16340011
DOI:
10.1074/jbc.M506850200
[Indexed for MEDLINE]
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