title: Mammalian target of rapamycin-independent S6K1 and 4E-BP1 phosphorylation during contraction in rat skeletal muscle.
abstract: Muscle protein synthesis rates decrease during contraction/exercise, but rapidly increase post-exercise. Previous studies mainly focused on signaling pathways that control protein synthesis during post-exercise recovery, such as mTOR and its downstream targets S6K1 and 4E-BP1. In this study, we investigated the effect of high-frequency electrical stimulation on the phosphorylation state of signaling components controlling protein synthesis in rat skeletal muscle. Electrical stimulation increased S6K1 Thr389 phosphorylation, which was unaffected by Torin1, a selective mTOR inhibitor, suggesting that S6K1 phosphorylation by contraction was mTOR-independent. Phosphorylation of eIF4B Ser422 was also increased during electrical stimulation, which was abrogated by inhibition of MEK/ERK/RSK1 activation. Moreover, although phosphorylation of conventional mTOR sites in 4E-BP1 decreased during contraction, mTOR-independent phosphorylation was also apparent, which was associated with the release of 4E-BP1 from eIF4E. The results indicate mTOR-independent phosphorylation of S6K1 and 4E-BP1 and suggest MEK/ERK/RSK1-dependent phosphorylation of eIF4B during skeletal muscle contraction. These phosphorylation events would keep the translation initiation machinery "primed" in an active state so that protein synthesis could quickly resume post-exercise.
authors.affiliation: Université catholique de Louvain and de Duve Institute, Avenue Hippocrate 75, B-1200 Brussels, Belgium.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Didier
authors.initials: D
authors.lastname: Vertommen
authors.forename: Mark H
authors.initials: MH
authors.lastname: Rider
authors.forename: Yu-Chiang
authors.initials: YC
authors.lastname: Lai
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System; D008297:Male; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D014176:Protein Biosynthesis; D051381:Rats; D017208:Rats, Wistar; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D039561:Eukaryotic Initiation Factor-4E; D039642:Eukaryotic Initiation Factors; D047908:Intracellular Signaling Peptides and Proteins; C496896:Kcnn1 protein, rat; D010750:Phosphoproteins; D051640:Small-Conductance Calcium-Activated Potassium Channels; C031799:eIF-4B; C546845:mTOR protein, rat; D019893:Ribosomal Protein S6 Kinases; C526901:Rps6kb1 protein, rat; D058570:TOR Serine-Threonine Kinases