AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits.

Jonas T Treebak, Stephan Glund, Atul Deshmukh, Ditte K Klein, Yun Chau Long, Thomas E Jensen, Sebastian B Jørgensen, Benoit Viollet, Leif Andersson, Dietbert Neumann, Theo Wallimann, Erik A Richter, Alexander V Chibalin, Juleen R Zierath, Jørgen F P Wojtaszewski

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236 Citations (Scopus)

Abstract

AMP-activated protein kinase (AMPK) is a heterotrimeric protein that regulates glucose transport mediated by cellular stress or pharmacological agonists such as 5-aminoimidazole-4-carboxamide 1 beta-d-ribonucleoside (AICAR). AS160, a Rab GTPase-activating protein, provides a mechanism linking AMPK signaling to glucose uptake. We show that AICAR increases AMPK, acetyl-CoA carboxylase, and AS160 phosphorylation by insulin-independent mechanisms in isolated skeletal muscle. Recombinant AMPK heterotrimeric complexes (alpha1beta1gamma1 and alpha2beta2gamma1) phosphorylate AS160 in a cell-free assay. In mice deficient in AMPK signaling (alpha2 AMPK knockout [KO], alpha2 AMPK kinase dead [KD], and gamma3 AMPK KO), AICAR effects on AS160 phosphorylation were severely blunted, highlighting that complexes containing alpha2 and gamma3 are necessary for AICAR-stimulated AS160 phosphorylation in intact skeletal muscle. Contraction-mediated AS160 phosphorylation was also impaired in alpha2 AMPK KO and KD but not gamma3 AMPK KO mice. Our results implicate AS160 as a downstream target of AMPK.
Original languageEnglish
JournalDiabetes
Volume55
Issue number7
Pages (from-to)2051-8
Number of pages7
ISSN0012-1797
DOIs
Publication statusPublished - 2006

Bibliographical note

Keywords: Adenylate Kinase; Aminoimidazole Carboxamide; Animals; Biological Transport; Catalysis; GTPase-Activating Proteins; Glucose; Insulin; Kinetics; Mice; Mice, Knockout; Muscle, Skeletal; Phosphorylation; Protein Subunits; Ribonucleotides

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