Mammalian target of rapamycin-independent S6K1 and 4E-BP1 phosphorylation during contraction in rat skeletal muscle

• Published in: Cellular signalling 2013-09, Vol.25 (9), p.1877-1886
• Main Authors: Liu, Yang, Vertommen, Didier, Rider, Mark H., Lai, Yu-Chiang
• Format: Article
• Language: English
• Subjects: 4E-BP1; Activation; AMPK; Animals; Carrier Proteins - metabolism; Cellular; Contraction; eIF4B; Eukaryotic Initiation Factor-4E - metabolism; Eukaryotic Initiation Factors - metabolism; Inhibitors; Male; MAP Kinase Signaling System; Muscle Contraction; Muscle, Skeletal - physiology; Muscles; Phosphoproteins - metabolism; Phosphorylation; Protein Biosynthesis; Protein synthesis; Rats; Rats, Wistar; Ribosomal Protein S6 Kinases - metabolism; S6K1; Small-Conductance Calcium-Activated Potassium Channels - metabolism; Stimulation; TOR Serine-Threonine Kinases - metabolism; Translations
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2013.05.005

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. •Muscle contraction increases S6K1 and 4E-BP1 phosphorylation independent of mTORC1.•Contraction-induced 4E-BP1 phosphorylation is associated with release from eIF4E.•Contraction increases eIF4B phosphorylation via MEK/ERK/RSK1.