title: Exercise rapidly increases eukaryotic elongation factor 2 phosphorylation in skeletal muscle of men.
abstract: Protein synthesis in skeletal muscle is known to decrease during contractions but the underlying regulatory mechanisms are unknown. Here, the effect of exercise on skeletal muscle eukaryotic elongation factor 2 (eEF2) phosphorylation, a key component in protein translation machinery, was examined. Eight healthy men exercised on a cycle ergometer at a workload eliciting approximately 67% peak pulmonary oxygen consumption (VO2 peak) with skeletal muscle biopsies taken from the vastus lateralis muscle at rest as well as after 1, 10, 30, 60 and 90 min of exercise. In response to exercise, there was a rapid (i.e. < 1 min) 5- to 7-fold increase in eEF2 phosphorylation at Thr56 that was sustained for 90 min of continuous exercise. The in vitro activity of skeletal muscle eEF2 kinase was not altered by exercise indicating that the increased activity of eEF2 kinase to eEF2 is not mediated by covalent mechanisms. In support of this, the increase in AMPK activity was temporally unrelated to eEF2 phosphorylation. However, skeletal muscle eEF2 kinase was potently activated by Ca(2)(+)-calmodulin in vitro, suggesting that the higher eEF2 phosphorylation in working skeletal muscle is mediated by allosteric activation of eEF2 kinase by Ca(2)(+) signalling via calmodulin. Given that eEF2 phosphorylation inhibits eEF2 activity and mRNA translation, these findings suggest that the inhibition of protein synthesis in contracting skeletal muscle is due to the Ca(2)(+)-induced stimulation of eEF2 kinase.
authors.affiliation: Copenhagen Muscle Research Centre, Institute of Exercise and Sport Sciences, Department of Human Physiology, Copenhagen University, Denmark. arose@ifi.ku.dk
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Rose
authors.forename: Christa
authors.initials: C
authors.lastname: Broholm
authors.forename: Kristian
authors.initials: K
authors.lastname: Kiillerich
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Finn
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Proud
authors.forename: Mark H
authors.initials: MH
authors.lastname: Rider
authors.forename: Erik A
authors.initials: EA
authors.lastname: Richter
authors.forename: Bente
authors.initials: B
authors.lastname: Kiens
mesh_terms: D000328:Adult; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D005080:Exercise Test; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000502:physiology*; D010766:Phosphorylation; D010807:Physical Endurance / Q000502:physiology*; D005082:Physical Exertion / Q000502:physiology*; D019892:eIF-2 Kinase / Q000378:metabolism*
chemical_list: D015852:Eukaryotic Initiation Factor-2; D009124:Muscle Proteins; D019892:eIF-2 Kinase