PMID- 16543272 OWN - NLM STAT- MEDLINE DCOM- 20060727 LR - 20211203 IS - 0022-3751 (Print) IS - 1469-7793 (Electronic) IS - 0022-3751 (Linking) VI - 573 IP - Pt 2 DP - 2006 Jun 1 TI - Exercise-induced alterations in extracellular signal-regulated kinase 1/2 and mammalian target of rapamycin (mTOR) signalling to regulatory mechanisms of mRNA translation in mouse muscle. PG - 497-510 AB - The present study examined the effects of an acute bout of treadmill exercise on signalling through the extracellular signal-regulated kinase (ERK)1/2 and mammalian target of rapamycin (mTOR) pathways to regulatory mechanisms involved in mRNA translation in mouse gastrocnemius muscle. Briefly, C57BL/6 male mice were run at 26 m min(-1) on a treadmill for periods of 10, 20 or 30 min, then the gastrocnemius was rapidly removed and analysed for phosphorylation and/or association of protein components of signalling pathways and mRNA translation regulatory mechanisms. Repression of global mRNA translation was suggested by disaggregation of polysomes into free ribosomes, which occurred by 10 min and was sustained throughout the time course. Exercise repressed the mTOR signalling pathway, as shown by dephosphorylation of the eukaryotic initiation factor (eIF)4E-binding protein-1 (4E-BP1), enhanced association of the regulatory-associated protein of mTOR with mTOR, and increased assembly of the tuberin-hamartin complex. In contrast, exercise caused no change in phosphorylation of either Akt/PKB or tuberin. Upstream of mTOR, exercise was associated with an increase in cAMP, protein kinase A activity, and AMP-activated protein kinase phosphorylation. Simultaneously, exercise caused a rapid and sustained activation of the MEK1/2-ERK1/2-p90RSK pathway, resulting in increased phosphorylation of downstream targets including eIF4E and the ribosomal protein (rp)S6 on S235/S236. Overall, the data are consistent with exercise-induced repression of mTOR signalling and global rates of mRNA translation, accompanied perhaps by up-regulated translation of selected mRNAs through regulatory mechanisms such as eIF4E and rpS6 phosphorylation, mediated by activation of the ERK1/2 pathway. FAU - Williamson, David L AU - Williamson DL AD - Department of Cellular and Molecular Physiology, H166 The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. FAU - Kubica, Neil AU - Kubica N FAU - Kimball, Scot R AU - Kimball SR FAU - Jefferson, Leonard S AU - Jefferson LS LA - eng GR - F32 DK067803/DK/NIDDK NIH HHS/United States GR - R01 DK015658/DK/NIDDK NIH HHS/United States GR - DK15658/DK/NIDDK NIH HHS/United States GR - DK67803/DK/NIDDK NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20060316 PL - England TA - J Physiol JT - The Journal of physiology JID - 0266262 RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) SB - IM CIN - J Physiol. 2006 Jun 1;573(Pt 2):288-9. PMID: 16600996 MH - Animals MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mitogen-Activated Protein Kinase 1/*metabolism/physiology MH - Mitogen-Activated Protein Kinase 3/*metabolism/physiology MH - Muscle, Skeletal/*enzymology/physiology MH - Physical Conditioning, Animal MH - Protein Biosynthesis/*physiology MH - Protein Kinases/genetics/*metabolism MH - Signal Transduction/*genetics MH - TOR Serine-Threonine Kinases PMC - PMC1779730 EDAT- 2006/03/18 09:00 MHDA- 2006/07/28 09:00 PMCR- 2007/06/01 CRDT- 2006/03/18 09:00 PHST- 2006/03/18 09:00 [pubmed] PHST- 2006/07/28 09:00 [medline] PHST- 2006/03/18 09:00 [entrez] PHST- 2007/06/01 00:00 [pmc-release] AID - jphysiol.2005.103481 [pii] AID - 10.1113/jphysiol.2005.103481 [doi] PST - ppublish SO - J Physiol. 2006 Jun 1;573(Pt 2):497-510. doi: 10.1113/jphysiol.2005.103481. Epub 2006 Mar 16.