Predominant alpha2/beta2/gamma3 AMPK activation during exercise in human skeletal muscle

J Physiol. 2006 Dec 15;577(Pt 3):1021-32. doi: 10.1113/jphysiol.2006.120972. Epub 2006 Oct 12.


5'AMP-activated protein kinase (AMPK) is a key regulator of cellular metabolism and is regulated in muscle during exercise. We have previously established that only three of 12 possible AMPK alpha/beta/gamma-heterotrimers are present in human skeletal muscle. Previous studies describe discrepancies between total AMPK activity and regulation of its target acetyl-CoA-carboxylase (ACC)beta. Also, exercise training decreases expression of the regulatory gamma3 AMPK subunit and attenuates alpha2 AMPK activity during exercise. We hypothesize that these observations reflect a differential regulation of the AMPK heterotrimers. We provide evidence here that only the alpha2/beta2/gamma3 subunit is phosphorylated and activated during high-intensity exercise in vivo. The activity associated with the remaining two AMPK heterotrimers, alpha1/beta2/gamma1 and alpha2/beta2/gamma1, is either unchanged (20 min, 80% maximal oxygen uptake ) or decreased (30 or 120 s sprint-exercise). The differential activity of the heterotrimers leads to a total alpha-AMPK activity, that is decreased (30 s trial), unchanged (120 s trial) and increased (20 min trial). AMPK activity associated with the alpha2/beta2/gamma3 heterotrimer was strongly correlated to gamma3-associated alpha-Thr-172 AMPK phosphorylation (r(2) = 0.84, P < 0.001) and to ACCbeta Ser-221 phosphorylation (r(2) = 0.65, P < 0.001). These data single out the alpha2/beta2/gamma3 heterotrimer as an important actor in exercise-regulated AMPK signalling in human skeletal muscle, probably mediating phosphorylation of ACCbeta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Acetyl-CoA Carboxylase / chemistry
  • Acetyl-CoA Carboxylase / metabolism
  • Adult
  • Exercise / physiology*
  • Humans
  • Male
  • Multienzyme Complexes / metabolism*
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / physiology*
  • Phosphorylation
  • Physical Endurance
  • Protein Kinases / chemistry
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Serine / metabolism
  • Signal Transduction
  • Threonine / metabolism
  • Time Factors


  • Multienzyme Complexes
  • Threonine
  • Serine
  • Protein Kinases
  • PRKAA1 protein, human
  • PRKAA2 protein, human
  • PRKAB2 protein, human
  • PRKAG1 protein, human
  • PRKAG3 protein, human
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Acetyl-CoA Carboxylase