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

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• 作者：Yang Liu ; Didier Vertommen ; Mark H. Rider ; Yu-Chiang Lai
• 关键词：4E-BP1 ; eukaryotic initiation factor 4E-binding protein 1 ; AMPK ; AMP-activated protein kinase ; eEF2 ; eukaryotic elongation factor 2 ; eIF ; eukaryotic initiation factor ; ERK ; extracellular-signal-regulated kinase ; MEK ; mitogen-activated protein kinase/extra
• 刊名：Cellular Signalling
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：25
• 期：9
• 页码：1877-1886
• 全文大小：758 K

文摘

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.