AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits.
- Additional Document Info
- View All
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.
author list (cited authors)
Treebak, J. T., Glund, S., Deshmukh, A., Klein, D. K., Long, Y. C., Jensen, T. E., ... Wojtaszewski, J.
complete list of authors
Treebak, Jonas T||Glund, Stephan||Deshmukh, Atul||Klein, Ditte K||Long, Yun Chau||Jensen, Thomas E||Jørgensen, Sebastian B||Viollet, Benoit||Andersson, Leif||Neumann, Dietbert||Wallimann, Theo||Richter, Erik A||Chibalin, Alexander V||Zierath, Juleen R||Wojtaszewski, Jørgen FP