Premium
Exercise rapidly increases eukaryotic elongation factor 2 phosphorylation in skeletal muscle of men
Author(s) -
Rose Adam J.,
Broholm Christa,
Kiillerich Kristian,
Finn Stephen G.,
Proud Christopher G.,
Rider Mark H.,
Richter Erik A.,
Kiens Bente
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.097154
Subject(s) - skeletal muscle , phosphorylation , protein kinase a , biology , kinase , calmodulin , medicine , endocrinology , chemistry , microbiology and biotechnology , biochemistry , enzyme
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 ∼67% peak pulmonary oxygen consumption 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.