Skip to main content
SpringerLink
Log in

Mechanical stimuli of skeletal muscle: implications on mTOR/p70s6k and protein synthesis

  • Invited Review
  • Published:
European Journal of Applied Physiology Aims and scope Submit manuscript

Abstract

The skeletal muscle is a tissue with adaptive properties which are essential to the survival of many species. When mechanically stimulated it is liable to undergo remodeling, namely, changes in its mass/volume resulting mainly from myofibrillar protein accumulation. The mTOR pathway (mammalian target of rapamycin) via its effector p70s6k (ribosomal protein kinase S6) has been reported to be of importance to the control of skeletal muscle mass, particularly under mechanical stimulation. However, not all mechanical stimuli are capable of activating this pathway, and among those who are, there are differences in the activation magnitude. Likewise, not all skeletal muscle fibers respond to the same extent to mechanical stimulation. Such evidences suggest specific mechanical stimuli through appropriate cellular signaling to be responsible for the final physiological response, namely, the accumulation of myofibrillar protein. Lately, after the mTOR signaling pathway has been acknowledged as of importance for remodeling, the interest for the mechanical/chemical mediators capable of activating it has increased. Apart from the already known MGF (mechano growth factor), some other mediators such as phosphatidic acid (PA) have been identified. This review article comprises and discusses relevant information on the mechano-chemical transduction of the pathway mTOR, with especial emphasis on the muscle protein synthesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Almon RR, Dubois DC (1988) Adrenalectomy eliminates both fiber-type differences and starvation effects on denervated muscle. Am J Physiol 225:E850–E856

    Google Scholar 

  • Almon RR, Dubois DC (1990) Fiber-type discrimination in disuse and glucocorticoid induced atrophy. Med Sci Sports Exerc 22:304–311

    PubMed  CAS  Google Scholar 

  • Aoki MS, Myiabara EH, Soares AG, Saito ET, Moriscot AS (2006) mTOR pathway inhibition attenuates skeletal muscle growth induced by stretching. Cell Tissue Res 324:149–156

    Article  PubMed  CAS  Google Scholar 

  • Atherton PJ, Babraj J, Smith K, Singh J, Rennie MJ, Wackerhage H (2005) Selective activation of AMPK-PGC-1alpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation. FASEB J 19:786–798

    PubMed  CAS  Google Scholar 

  • Baar K, Esser K (1999) Phosphorylation of p70(S6k) correlates with increased skeletal muscle mass following resistance exercise. Am J Physiol 45:C120-C127

    Google Scholar 

  • Balagopal P, Schimke JC, Ades PA, Adey DB, Nair KS (2001) Age effect on transcript levels and synthesis rate of muscle MHC and response to resistance exercise. Am J Physiol 280:E203–E208

    CAS  Google Scholar 

  • Barton-Davis E, Shoturma DI, Musaro A, Rosenthal N, Sweeney Hl (1998) Viral mediated expression of insulin-like growth factor-1 blocks the aging-related loss of skeletal muscle function. Proc Natl Acad Sci USA 95:15603–15607

    Article  PubMed  CAS  Google Scholar 

  • Bloch RJ, Gonzalez-Serratos H (2003) Lateral force transmission across costameres in skeletal muscle. Exerc Sport Sci Rev 31:73–78

    Article  PubMed  Google Scholar 

  • Blomstrand E, Eliasson J, Karlsson HK, Kohnke R. (2006) Branched chain amino acids activate key enzymes in protein synthesis after physical exercise. J Nutr 136:269S–273S

    PubMed  CAS  Google Scholar 

  • Bodine SC (2006) mTOR signaling and the molecular adaptation to resistance exercise. Med Sci Sports Exerc 38:1950–1957

    Article  PubMed  CAS  Google Scholar 

  • Bodine SC, Stitt TN, Gonzalez M, Kline WO, Stover GL, Bauerlein R, Zlotchenko E, Scrimgeour A, Lawrence JC, Glass DJ, Yancopoulos GD (2001) Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol 3:1014–1019

    Article  PubMed  CAS  Google Scholar 

  • Bolster DR, Crozier SJ, Kimball SR, Jefferson LS (2002) AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through downregulated mTOR signalling J Biol Chem 277:23977–23980

    Article  PubMed  CAS  Google Scholar 

  • Bolster DR, Kubica N, Crozier SJ, Williamson DL, Farrell PA, Kimball SR, Jefferson LS (2003) Immediate response of mammalian target of rapamycin (mTOR)-mediated signalling following acute resistance exercise in rat skeletal muscle. J Physiol 15:213–220

    Article  Google Scholar 

  • Booth FW, Baldwin KM (1966) Muscle plasticity: energy demand and supply processes. In: Rowell LB, Shepard JT (eds) Handbook of physiology. Oxford University Press, New York, pp 1074–1123

    Google Scholar 

  • Boppart MD, Burkin DJ, Kaufman SJ (2006) Alpha7beta1-integrin regulates mechanotransduction and prevents skeletal muscle injury. Am J Physiol 290:C1660–C1665

    Article  CAS  Google Scholar 

  • Carraro F, Stuart CA, Hartl WH, Rosenblatt J, Wolfe RR (1990) Effect of exercise and recovery on muscle protein synthesis in human subjects. Am J Physiol 259:E470–E476

    PubMed  CAS  Google Scholar 

  • Chen J (2004) Novel regulatory mechanisms of mTOR signaling. Curr Top Microbiol Immunol 279:245–257

    PubMed  CAS  Google Scholar 

  • Chiang GC, Abraham RT (2005) Phosphorylation of mammalian target of rapamycin (mTOR) at Ser-2448 is mediated by p70s6 kinase. J Biol Chem 280:25485–25490

    Article  PubMed  CAS  Google Scholar 

  • Coffey VG, Zhong Z, Shield A, Canny BJ, Chibalin AV, Zierath JR, Hawley JA (2005) Early signaling responses to divergent exercise stimuli in skeletal muscle from well-trained humans. FASEB J 20:190–200

    PubMed  Google Scholar 

  • Cuthberson DJ, Babraj J, Smith K, Wilkes E, Fedele MJ, Esser K, Rennie M (2006) Anabolic signaling and protein synthesis in human skeletal muscle after dynamic shortenin or lengthening exercise. Am J Physiol 290:E731–E738

    Google Scholar 

  • De Keulenaer GW, Chappell DC, Ishizaka N, Nerem RM, Alexander RW, Griendling KK (1998) Oscillatory and steady laminar shear stress differentially affect human endothelial redox state: role of a superoxide-producing NADH oxidase. Circ Res 82:1094–101

    PubMed  Google Scholar 

  • Deshmukh A, Coffey VG, Zhong Z, Chibalin AV, Hawley JÁ, Zierath JR (2006) Exercise-induced phosprolylation of the novel Akt substrates AS 160 and filamin A in human skeletal muscle. Diabetes 55:1776–1782

    Article  PubMed  CAS  Google Scholar 

  • Dreyer HC, Fujita S, Cadenas J, Chinkes DL, Volpi E, Rasmussen BB (2006) Resistance exercise increases AMPK activity and reduces 4E-BP1 phosphorylation and protein synthesis in human skeletal muscle. J Physiol 576:613–624

    Article  PubMed  CAS  Google Scholar 

  • Eliasson J, Elfegoun T, Nilsson J, Kohnke R, Ekblom B, Blomstrand E (2006) Maximal lengthening contractions increase p70s6k kinase phosphorylation in human skeletal muscle in the absence of nutritional supply. Am J Physiol 291:E1197–E1205

    CAS  Google Scholar 

  • Ervasti JM (2003) Costameres: the Achilles’ heel of Herculean muscle. J Biol Chem 278: 13591–13594

    Article  PubMed  CAS  Google Scholar 

  • Fang Y, Park IH, Wu AL, Du G, Huang P, Frohman MA, Huang P, Frohman MA, Brown HA, Chen J (2003) PLD1 regulates mTOR signaling and mediates Cdc42 activation of S6K1. Curr Biol 13:2037–2044

    Article  PubMed  CAS  Google Scholar 

  • Fleck SJ, Kraemer WJ (1997) Muscle physiology. In: Designing resistance training programs. Human kinetics, Ilinois, pp 45–63

  • Fry AC (2004) The role of resistance exercise intensity on muscle fibre adaptations. Sports Med 34:663–679

    Article  PubMed  Google Scholar 

  • Fujita S, Abe T, Drummond MJ, Cadenas JG, Dreyer HC, Sato Y, Volpi E, Rasmussen BB (2007) Blood flow restriction during low-intensity resistance exercise increases S6K1 phosphorylation and muscle protein synthesis. J Appl Physiol 103:903–910

    Article  PubMed  CAS  Google Scholar 

  • Glick Z, Mcnurlan MA, Garlick PJ (1982) Protein synthesis rate in liver and muscle of rats following four days of overfeeding. J Nutr 112:391–397

    PubMed  CAS  Google Scholar 

  • Goldberg AL (1967) Protein synthesis in tonic and phasic skeletal muscles. Nature 216:1219–1220

    Article  PubMed  CAS  Google Scholar 

  • Goldberg AL, Etlinger JD, Goldspink DF, Jablecky C (1975) Mechanism of workinduced hypertrophy of skeletal muscle. Med Sci Sports 7:185–198

    PubMed  CAS  Google Scholar 

  • Goldspink G (1999) Changes in muscle mass and phenotype and the expression of autocrine and systemic growth factors by muscle in response to stretch and overload. J Anat 194:323–334

    Article  PubMed  CAS  Google Scholar 

  • Goldspink G (2002) Gene expression in skeletal muscle. Biochem Soc Trans 30:285– 290

    Article  PubMed  CAS  Google Scholar 

  • Goldspink G, Booth F (1992) General remarks: mechanical signals and gene expression in muscle. Am J Physiol 262:R327–R328

    Google Scholar 

  • Goldspink G, Yang SY (2001) Method of treating muscular disorders. United States Patent. Patent N° US 6,221,842 B1, April 24

  • Grounds MD, Sorokin L, White J (2005) Strength at the extracellular matrix–muscle interface. Scand J Med Sci Sports 15:347–358

    Article  Google Scholar 

  • Haddad F, Adams GR (2002) Selected contribution: acute cellular and molecular responses to resistance exercise. J Appl Physiol 93:393–403

    Google Scholar 

  • Hameed M, Orrell RW, Cobbold M, Goldspink G, Harridge SDR (2003) Expression of IGF-1 splice variants in young and old human skeletal muscle after high resistance exercise. J Physiol 547:247–254

    Article  PubMed  CAS  Google Scholar 

  • Hasten DL, Pak-Loduca KA, Obert KE, Yarasheski KE (2000) Resistance exercise acutely increases MHC and mixed muscle protein synthesis rates in 78–84 and 23–32 yr olds. Am J Physiol 278:E620–E626

    CAS  Google Scholar 

  • Hernandez JM, Fedele MJ, Farrell PA (2000) Time course evaluation of protein synthesis and glucose uptake after acute resistance exercise in rats. J Appl Physiol 88:1142–1149

    PubMed  CAS  Google Scholar 

  • Holz MK, Blenis J (2005) Identification of S6 kinase 1 as a novel mammalian target of rapamycin (mTOR)- phosphorylating kinase. J Biol Chem 280:26089–26093

    Article  PubMed  CAS  Google Scholar 

  • Hong JH, Oh SO, Lee M, Kim YR, Kim DU, Hur GM, Lee JH, Lim K, Hwang BD, Park SK (2001) Enhancement of lysophosphatidic acid-induced ERK phosphorylation by phospholipase D1 via the formation of phosphatidic acid. Biochem Biophys Res Commun 281:1337–1342

    Article  PubMed  CAS  Google Scholar 

  • Hornberger TA, Chien S (2006) Mechanical stimuli and nutrients regulate rapamycin-sensitive signaling through distinct mechanisms in skeletal muscle. J Cell Biochem 97:1207–1216

    Article  PubMed  CAS  Google Scholar 

  • Hornberger TA, McLoughlin TJ, Leszczynski JK, Armstrong DD, Jameson RR, Bowen PE, Hwang ES, Hou H, Moustafa ME, Carlson BA, Hatfield DL, Diamond AM, Esser KA (2003) Selenoprotein-deficient transgenic mice exhibit enhanced exercise-induced muscle growth. J Nutr 133:3091–3097

    PubMed  CAS  Google Scholar 

  • Hornberger TA, Armstrong DD, Koh TJ, Burkholder TJ, Esser K (2005) Intracellular signaling specificity in response to uniaxial vs. multiaxial stretch: implications for mechanotransduction. Am J Physiol 288:C185–C194

    CAS  Google Scholar 

  • Hornberger TA, Stuppard R, Conley KE, Fedele MJ, Fiorotto ML, Chin ER, Esser KA (2004) Mechanical stimuli regulate rapamycin sensitive signaling by a phosphoinositide 3-kinase-, protein kinase B- and growth factor-independent mechanism. Biochem J 380:795–804

    Article  PubMed  CAS  Google Scholar 

  • Hornberger TA, Mak YW, Hsiung JW, Huang SA, Chien S (2006a) The role of phospholipase D and phosphatidic acid in the mechanical activation of mTOR signaling in skeletal muscle. Proc Natl Acad Sci USA 103:4741–4746

    Article  PubMed  CAS  Google Scholar 

  • Hornberger TA, Sukhija KB, Chien S (2006b) Regulation of mTOR by mechanically induced signaling events in skeletal muscle. Cell Cycle 13:1391–1396

    Google Scholar 

  • Ingber DE (2006) Cellular mechanotransduction: putting all the pieces together again. FASEB J 20:811–827

    Article  PubMed  CAS  Google Scholar 

  • Jacinto E, Hall MN (2003) Tor signalling in bugs, brain and brawn. Nat Rev Mol Cell Biol 4:117–126

    Article  PubMed  CAS  Google Scholar 

  • Kam Y, Exton JH (2004) Role of phospholipase D1 in the regulation of mTOR activity by lysophosphatidic acid. FASEB J 18:311–319

    Article  PubMed  CAS  Google Scholar 

  • Karlsson HK, Nilsson PA, Nilsson J, Chibalin AV, Zierath JR, Blomstrand E (2004). Branched-chain amino acids increase p70s6k phosphosphorylation in human skeletal muscle after resistance exercise. Am J Physiol 287:E1–E7

    Article  CAS  Google Scholar 

  • King WG, Mattaliano MD, Chan TO, Tsichlis PN, Brugge JS (1997) Phosphatidylinositol 3-kinase is required for integrin-stimulated akt and raf-1/mitogen-activated protein kinase pathway activation. Mol Cell Biol 17:4406–4418

    PubMed  CAS  Google Scholar 

  • Koopman R, Zorenc AHG, Gransier RJJ, Cameron-Smith D, Van Loon LJC (2006) Increase in S6K1 phosphorylation in human skeletal muscle following resistance exercise occurs mainly in type II muscle fibers. Am J Physiol 290:E1245–E1252

    CAS  Google Scholar 

  • Kubica N, Bolster D, Farrell PA, Kimball SR, Jefferson L (2005) Resistance exercise increases muscle protein synthesis and translation of eukaryotic initiation factor 2Be mRNA in a mammalian target of rapamycin-dependent manner. J Biol Chem 280:7570–7580

    Article  PubMed  CAS  Google Scholar 

  • Lai KM, Gonzalez M, Poueymirou WT, Kline WO, Na E, Zlotchenko E, Stitt TN, Economides AN, Yancopoulos GD, Glass DJ (2004) Conditional activation of Akt in adult skeletal muscle induces rapid hypertrophy. Mol Cell Biol 24:9295–9304

    Article  PubMed  CAS  Google Scholar 

  • Lawrence JC, Abraham RT (1997) PHAS/4E-BPs as regulators of mRNA translation and cell proliferation. Trends Biochem Sci 22:345–349

    Article  PubMed  CAS  Google Scholar 

  • Lee S, Park JB, Kim JH, Kim Y, Kim JH, Shin KJ, Lee JS, Ha SH, Suh PG, Ryu SH (2001) Actin directly interacts with phospholipase D, inhibiting its activity. J Biol Chem 276:28252–28260

    Article  PubMed  CAS  Google Scholar 

  • Malik RK, Parsons JT (1996) Integrin-dependent activation of the ribosomal s6 kinase signaling pathway. J Biol Chem 271:29785–29791

    Article  PubMed  CAS  Google Scholar 

  • Mascher H, Andersson H, Nilsson PA, Ekblom B, Blomstrand E (2007) Changes in signaling pathways regulating protein synthesis in human muscle in the recovery period after endurance exercise. Acta Physiol 191:67–75

    Article  CAS  Google Scholar 

  • Mayer U (2003) Integrins: redundant or important players in skeletal muscle? J Biol Chem 278:14587–14590

    Article  PubMed  CAS  Google Scholar 

  • McKoy G, Ashley W, Mander J, Yang SY, Williams N, Russell B, Goldspink G (1999) Expression of insulin growth factor-1 splice variants and structural genes in rabbit skeletal muscle induced by stretch and stimulation. J Physiol 516:583–592

    Article  PubMed  CAS  Google Scholar 

  • Meyuhas O (2000) Synthesis of the translational apparatus is regulated at the translational level. Eur J Biochem 267:6321–6330

    Article  PubMed  CAS  Google Scholar 

  • Mittendorfer B, Andersen JL, Plomgaard P, Saltin B, Babraj JA, Smith K, Rennie MJ (2005) Protein synthesis rates in human muscles: neither anatomical location nor fibre-type composition are major determinants. J Physiol 563:203–211

    Article  PubMed  CAS  Google Scholar 

  • Nader GA, Esser K (2001) Intracellular signaling specificity in skeletal muscle in response to different modes of exercise. J Appl Physiol 90:1936–1942

    PubMed  CAS  Google Scholar 

  • Nader GA, McLoughlin TJ, Esser KA (2005) mTOR function in skeletal muscle hypertrophy: increased ribosomal RNA via cell cycle regulators. Am J Physiol 289:C1457–C1465

    Article  CAS  Google Scholar 

  • Nave BT, Ouwens DJ, Withers DR, Shepherd A, Shepherd PR (1999) Mammalian target of rapamycin is a direct target for protein kinase B: identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation. Biochem J 344:427–431

    Article  PubMed  CAS  Google Scholar 

  • Ohanna M, Sobering AK, Lapointe T, Lorenzo L, Praud C, Petroulakis E, Sonenberg N, Kelly PA, Sotiropoulos A, Pende M (2005) Atrophy of S6k1 −/− skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control. Nat Cell Biol 7:286–294

    Article  PubMed  CAS  Google Scholar 

  • Pallafacchina G, Calabria E, Serrano A, Kalhovde JM, Schiaffino S (2002) A protein kinase B-dependent and rapamycin sensitive pathway controls skeletal muscle growth but not fiber type specification. Proc Natl Acad Sci USA 99:9213–9218

    Article  PubMed  CAS  Google Scholar 

  • Park JB, Kim JH, Kim Y, Há SH, Yoo JS, Du G, Frohman MA, Suh PG, Ryu SH (2000) Cardiac phospholipase D2 localizes to sarcolemmal membranes and is inhibited by alpha-actinin in an ADP-ribosylation factor-reversible manner. J Biol Chem 275:21295–21301

    Article  PubMed  CAS  Google Scholar 

  • Parkington JD, Siebert AP, Lebrasseur NK, Fielding RA (2003) Differential activation of mTOR signaling by contractile activity in skeletal muscle. Am J Physiol 285:R1086–R1090

    CAS  Google Scholar 

  • Peterson RT, Beal PA, Comb MJ, Schreiber SL (2000) FKBP12-Rapamycin-associated protein (FRAP) autophosphorylates at serine 2481 under translationally repressive conditions. J Biol Chem 275:7416–7423

    Article  PubMed  CAS  Google Scholar 

  • Phillips SM, Parise G, Roy BD, Tipton KD, Wolfe RR, Tarnopolsky MA (2002) Resistance-training-induced adaptations in skeletal muscle protein turnover in fed state. Can J Physiol Pharmacol 80:1045–1053

    Article  PubMed  CAS  Google Scholar 

  • Pullen N, Thomas G (1997) The modular phosphorylation and activation of p70s6k. FEBS Lett 410:78–83

    Article  PubMed  CAS  Google Scholar 

  • Rasmussen BB, Phillips SM (2003) Contractile and nutritional regulation of human muscle growth. Exerc Sports Sci Rev 31:127–131

    Google Scholar 

  • Redpath NT, Price NT, Severinov KV, Proud GC (1993) Regulation of elongation factor-2 by multisite phosphorylation. Eur J Biochem 213:689–699

    Article  PubMed  CAS  Google Scholar 

  • Reiling JH, Sabatini DM (2006) Stress and mTORture signaling. Oncogene 25:6373–6383

    Article  PubMed  CAS  Google Scholar 

  • Rennie MJ (2005) Why muscle stops building when it’s working. J Physiol 569:3

    Article  PubMed  CAS  Google Scholar 

  • Rennie MJ, Wackerhage H (2003) Connecting the dots for mechanochemical transduction in muscle. J Physiol 553:1

    Article  PubMed  CAS  Google Scholar 

  • Reynolds TH, Bodine SC, Lawrence Jr JC (2002) Control of Ser 2448 phosphorylation in the mammalian target of rapamycin by insulin and skeletal muscle load. J Biol Chem 277:17657–17662

    Article  PubMed  CAS  Google Scholar 

  • Rommel C, Bodine SC, Clarke BA, Rossman R, Nunez L, Stitt TN, Yancopoulos GD, Glass DJ (2001) Mediation of IGF-1 induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol 3:1009–1013

    Article  PubMed  CAS  Google Scholar 

  • Russell B, Motlagh D, Ashley W (2000) Form follows function: how muscle shape is regulated by work. J Appl Physiol 88:1127–1132

    PubMed  CAS  Google Scholar 

  • Ruvinsky I, Meyuhas O (2006) Ribossomal protein S6 phosphorylation: from protein synthesis to cell size. Trends Biochem Sci 31:342–348

    Article  PubMed  CAS  Google Scholar 

  • Sakamoto K, Hirshman MF, Aschenbach WG, Goodyear LJ (2002) Contraction regulation of Akt in rat skeletal muscle. J Biol Chem 277:11910–11917

    Article  PubMed  CAS  Google Scholar 

  • Sakamoto K, Aschenbach WG, Hirshman MF, Goodyear LJ (2003) Akt signaling in skeletal muscle: regulation by exercise and passive stretch. Am J Physiol 285:E1081–E1088

    CAS  Google Scholar 

  • Sakamoto K, Arnolds DE, Ekberg I, Thorell A, Goodyear LJ (2004) Exercise regulates Akt, glycogen synthase kinase-3 activities in human skeletal muscle Biochem Biophys Res Commun 319:419–425

    Article  PubMed  CAS  Google Scholar 

  • Sarbassov D, Ali SM, Sabatini DM (2005) Growing roles for the mTOR pathway. Curr Opin Cell Biol17:596–603

    Article  Google Scholar 

  • Schmelzle T, Hall MN (2000) TOR, a central controller of cell growth. Cell 103:253–262

    Article  PubMed  CAS  Google Scholar 

  • Scott PH, Brunn GJ, Konh AD, Roth RA, Lawrence Jc-JR (1998) Evidence of insulin-stimulated phosphorylation and activation of the mammalian target of rapamycin mediated by a protein kinase B signaling pathway. Proc Natl Acad Sci USA 95:7772–7777

    Article  PubMed  CAS  Google Scholar 

  • Sheffield-Moore M, Yeckel CW, Volpi et al\ (2004) Post exercise protein metabolism in older and younger men following moderate intensity aerobic exercise. Am J Physiol 287:E513–E522

    Google Scholar 

  • Stokoe D, Stephens LR, Copeland T, Gaffney PR, Reese CB, Painter GF, Holmes AB, Mccormick F, Hawkins PT (1997) Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. Science 277:567–701

    Article  PubMed  CAS  Google Scholar 

  • Thiimmaiah KL, Easton JB, Germain GS, Morton CL, Kamath S, Buolamwini JK, Houghton PJ (2005) Identification of N10-substituted phenoxazines as potent and specific inhibitors of Akt signaling. J Biol Chem 280:31924–31935

    Article  Google Scholar 

  • Tidball JG (2005) Mechanical signal transduction in skeletal muscle growth and adaptation. J Appl Physiol 98:1900–1908

    Article  PubMed  CAS  Google Scholar 

  • Timson BF (1990) Evaluation of animal models for the study of exercise-induced muscle enlargement. J Appl Physiol 69:1935–1945

    PubMed  CAS  Google Scholar 

  • Turinsky J, Damrau-Abney A (1999) Akt kinases and 2-deoxyglucose uptake in rat skeletal muscles in vivo: study with insulin and exercise. Am J Physiol 276:R277–R282

    PubMed  CAS  Google Scholar 

  • Wackerhage H, Rennie MJ (2006) How nutrition and exercise maintain the human musculoskeletal mass. J Anat 208:451–458

    Article  PubMed  CAS  Google Scholar 

  • Welle S, Bhatt K, Thornton CA (1999) Stimulation of myofibrillar synthesis by exercise is mediated by more efficient translation of mRNA. J Appl Physiol 86:1220–1225

    PubMed  CAS  Google Scholar 

  • Widrick JJ, Stelzer JE, Shoepe TC, Garner DP (2002) Functional properties of human muscle fibers after short-term resistance exercise training. Am J Physiol 283:R408–R416

    CAS  Google Scholar 

  • Wullschleger S, Loewith R, Hall MN (2006) TOR signaling in growth and metabolism. Cell 124:471–484

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Érico Chagas Caperuto for his critical reading of the manuscript and Maria Cristina Fioratti Florez for the careful specialized language revision of the present review article.

Author information

Authors and Affiliations

  1. Laboratory of Applied Nutrition and Metabolism, Physical Education and Sport School, University of São Paulo, Av. Prof. Mello Moraes, 65, PO Box 05508-900, São Paulo, SP, Brazil

    Nelo Eidy Zanchi & Antonio Herbert Lancha Jr

Authors
  1. Nelo Eidy Zanchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonio Herbert Lancha Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nelo Eidy Zanchi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zanchi, N.E., Lancha, A.H. Mechanical stimuli of skeletal muscle: implications on mTOR/p70s6k and protein synthesis . Eur J Appl Physiol 102, 253–263 (2008). https://doi.org/10.1007/s00421-007-0588-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-007-0588-3

Keywords

Search

Navigation