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

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.

published proceedings

  • Diabetes

altmetric score

  • 4

author list (cited authors)

  • Treebak, J. T., Glund, S., Deshmukh, A., Klein, D. K., Long, Y. C., Jensen, T. E., ... Wojtaszewski, J.

citation count

  • 214

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

publication date

  • July 2006