AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits.
2006 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 55, no 7, 2051-2058 p.Article in journal (Refereed) Published
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 (alpha 1 beta 1 gamma l and alpha 2 beta 2 gamma 1) phosphorylate AS160 in a cell-free assay. In mice deficient in AMPK signaling (alpha 2 AMPK knockout [KO], alpha 2 AMPK kinase dead [KD], and gamma 3 AMPK KO), AICAR effects on AS160 phosphorylation were severely blunted, highlighting that complexes containing alpha 2 and gamma 3 are necessary for AICAR-stimulated AS160 phosphorylation in intact skeletal muscle. Contraction-mediated AS160 phosphorylation was also impaired in alpha 2 AMPK KO and KD but not gamma 3 AMPK KO mice. Our results implicate AS160 as a downstream target of AMPK.
Place, publisher, year, edition, pages
2006. Vol. 55, no 7, 2051-2058 p.
Adenylate Kinase/deficiency/genetics/*metabolism, Aminoimidazole Carboxamide/analogs & derivatives/pharmacology, Animals, Biological Transport, Catalysis, GTPase-Activating Proteins/*metabolism, Glucose/metabolism, Insulin/pharmacology, Kinetics, Mice, Mice; Knockout, Muscle; Skeletal/*enzymology, Phosphorylation, Protein Subunits/metabolism, Ribonucleotides/pharmacology
Endocrinology and Diabetes
IdentifiersURN: urn:nbn:se:uu:diva-22548DOI: 10.2337/db06-0175ISI: 000238764600019PubMedID: 16804075OAI: oai:DiVA.org:uu-22548DiVA: diva2:50321