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.
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.
Williamson
David L
DL
Department of Cellular and Molecular Physiology, H166 The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Kubica
Neil
N
Kimball
Scot R
SR
Jefferson
Leonard S
LS
D000818:Animals; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism* / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism* / Q000502:physiology; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000502:physiology; D010805:Physical Conditioning, Animal; D014176:Protein Biosynthesis / Q000502:physiology*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases
D011494:Protein Kinases; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3