title: AS160 phosphorylation is associated with activation of alpha2beta2gamma1- but not alpha2beta2gamma3-AMPK trimeric complex in skeletal muscle during exercise in humans.
abstract: We investigated time- and intensity-dependent effects of exercise on phosphorylation of Akt substrate of 160 kDa (AS160) in human skeletal muscle. Subjects performed cycle exercise for 90 min (67% VO2 peak, n=8), 20 min (80% VO2 peak, n=11), 2 min (110% of peak work rate, n=9), or 30 s (maximal sprint, n=10). Muscle biopsies were obtained before, during, and after exercise. In trial 1, AS160 phosphorylation increased at 60 min (60%, P=0.06) and further at 90 min of exercise (120%, P<0.05). alpha2beta2gamma3-AMP-activated protein kinase (AMPK) activity increased significantly to a steady-state level after 30 min, whereas alpha2beta2gamma1-AMPK activity increased after 60 min of exercise with a further significant increase after 90 min. alpha2beta2gamma1-AMPK activity and AS160 phosphorylation correlated positively (r2=0.55). In exercise trials 2, 3, and 4, alpha2beta2gamma3-AMPK activity but neither AS160 phosphorylation nor alpha2beta2gamma1-AMPK activity increased. Akt Ser473 phosphorylation was unchanged in all trials, whereas Akt Thr308 phosphorylation increased significantly in trial 3 and 4 only. These results show that AS160 is phosphorylated in a time-dependent manner during moderate-intensity exercise and suggest that alpha2beta2gamma1- but not alpha2beta2gamma3-AMPK may act in a pathway responsible for exercise-induced AS160 phosphorylation. Furthermore, we show that AMPK complexes in skeletal muscle are activated differently depending on exercise intensity and duration.
authors.affiliation: Copenhagen Muscle Research Centre, Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, DK-2100, Copenhagen, Denmark.
authors.forename: Jonas T
authors.initials: JT
authors.lastname: Treebak
authors.forename: Jesper B
authors.initials: JB
authors.lastname: Birk
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Rose
authors.forename: Bente
authors.initials: B
authors.lastname: Kiens
authors.forename: Erik A
authors.initials: EA
authors.lastname: Richter
authors.forename: Jørgen F P
authors.initials: JF
authors.lastname: Wojtaszewski
mesh_terms: D055372:AMP-Activated Protein Kinases; D000328:Adult; D001706:Biopsy; D015444:Exercise / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; D009097:Multienzyme Complexes; C518767:TBC1D4 protein, human; D011494:Protein Kinases; D051058:Oncogene Protein v-akt; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases