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

被引：289
作者：
Horman, S
Vertommen, D
Heath, R
Neumann, D
Mouton, V
Woods, A
Schlattner, U
Walliman, T
Carling, D
Hue, L
Rider, MH
机构：
[1] Christian de Duve Inst Cellular Pathol, Hormone & Metab Res Unit, B-1200 Brussels, Belgium
[2] Catholic Univ Louvain, B-1200 Brussels, Belgium
[3] Hammersmith Hosp, Imperial Coll, Cellular Stress Grp, MRC,Clin Sci Ctr, London W12 0NN, England
[4] ETH, Inst Cell Biol, CH-8093 Zurich, Switzerland
来源：
JOURNAL OF BIOLOGICAL CHEMISTRY | 2006年 / 281卷 / 09期
基金：
英国医学研究理事会;
关键词：
D O I：
10.1074/jbc.M506850200
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 alpha 1-subunits. In perfused rat hearts, phosphorylation of the alpha 1/alpha 2 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.
引用
收藏
页码：5335 / 5340
页数：6
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