Predominant alpha2/beta2/gamma3 AMPK activation during exercise in human skeletal muscle.
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.
Birk
J B
JB
Copenhagen Muscle Research Centre, Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, 13 Universitetsparken, 2100 Copenhagen Ø, Denmark. jbirk@ifi.ku.dk
Wojtaszewski
J F P
JF
D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000737:chemistry / Q000378:metabolism; D000328:Adult; D015444:Exercise / Q000502:physiology*; D006801:Humans; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000502:physiology*; D010766:Phosphorylation; D010807:Physical Endurance; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D013912:Threonine / Q000378:metabolism; D013997:Time Factors
D009097:Multienzyme Complexes; D013912:Threonine; D012694:Serine; D011494:Protein Kinases; C526181:PRKAA2 protein, human; C526183:PRKAB2 protein, human; C526222:PRKAG1 protein, human; C526225:PRKAG3 protein, human; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human; D000103:Acetyl-CoA Carboxylase