Mitogen-activated protein kinase signal transduction in skeletal muscle: Effects of exercise and muscle contraction

Acta Physiologica Scandinavica

Volumn 172, Issue 3, 2001, Pages 227-238

  Widegren, U ^b   Ryder, J W ^b   Zierath, J R ^a,b  

^a KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^b KAROLINSKA INSTITUTE   (Sweden)

Author keywords

Exercise; Extracellular signal regulated kinase; Gene expression; Mitogen activated protein kinase; Muscle contraction; Stress activated protein kinase

Indexed keywords

MITOGEN ACTIVATED PROTEIN KINASE;

ANIMAL; EXERCISE; HUMAN; METABOLISM; MUSCLE CONTRACTION; PHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION; SKELETAL MUSCLE;

ANIMALS; EXERCISE; EXERTION; HUMANS; MITOGEN-ACTIVATED PROTEIN KINASES; MUSCLE CONTRACTION; MUSCLE, SKELETAL; SIGNAL TRANSDUCTION;

EID: 0035406554     PISSN: 00016772     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1365-201x.2001.00855.x     Document Type: Article

References (102)

1. Aikawa, R., Komuro, I., Yamazaki, T. et al. 1997. Oxidative stress activates extracellular signal-regulated kinases through Src and Ras in cultured cardiac myocytes of neonatal rats. J Clin Invest 100, 1813-1821.
2. Anderson, N.G., Maller, J.L., Tonks, N.K. & Sturgill, T.W. 1990. Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase. Nature 343, 651-653.
3. Armstrong, R.B. & Laughlin, M.H. 1984. Exercise blood flow patterns within and among rat muscles after training. Am J Physiol 246, H59-H68.
4. Aronson, D., Dufresne, S.D. & Goodyear, L.J. 1997a. Contractile activity stimulates the c-Jun NH2-terminal kinase pathway in rat skeletal muscle. J Biol Chem 272, 25 636-25 640.
5. Aronson, D., Violan, M.A., Dufresne, S.D., Zangen, D., Fielding, R.A. & Goodyear, L.J. 1997b. Exercise stimulates the mitogen-activated protein kinase pathway in human skeletal muscle. J Clin Invest 99, 1251-1257.
6. Aronson, D., Boppart, M.D., Dufresne, S.D., Fielding, R.A. & Goodyear, L.J. 1998a. Exercise stimulates c-Jun NH2 kinase activity and c-Jun transcriptional activity in human skeletal muscle. Biochem Biophys Res Commun 251, 106-110.
7. Aronson, D., Wojtaszewski, J.F., Thorell, A., Nygren, J., Zangen, D., Richter, E.A., Ljungqvist, O., Fielding, R.A. & Goodyear, L.J. 1998b. Extracellular-regulated protein kinase cascades are activated in response to injury in human skeletal muscle. Am J Physiol 275, C555-C561.
8. Bergstrom, J., Hermansen, L., Hultman, E. & Saltin, B. 1967. Diet, muscle glycogen and physical performance. Acta Physiol Scand 71, 140-150.
9. Beyaert, R., Cuenda, A., Vanden Berghe, W., Plaisance, S., Lee, J.C., Haegeman, G., Cohen, P. & Fiers, W. 1996. The p38/RK mitogen-activated protein kinase pathway regulates interleukin-6 synthesis response to tumor necrosis factor. Embo J 15, 1914-1923.
10. Booth, F.W. & Thomason, D.S. 1991. Molecular and cellular adaptation of muscle in response to exercise: perspectives of various models. Physiol Rev 71, 541-585.
11. Boppart, M.D., Aronson, D., Gibson, L., Roubenoff, R., Abad, L.W., Bean, J., Goodyear, L.J. & Fielding, R.A. 1999. Eccentric exercise markedly increases c-Jun NH (2) - terminal kinase activity in human skeletal muscle. J Appl Physiol 87, 1668-1673.
12. Boppart, M.D., Asp, S., Wojtaszewski, J.F., Fielding, R.A., Mohr, T. & Goodyear, L.J. 2000. Marathon running transiently increases c-Jun NH2-terminal kinase and p38 activities in human skeletal muscle. J Physiol (Lond) 526, 663-669.
13. Boulton, T.G., Nye, S.H., Robbins, D.J., Ip, N.Y., Radziejewska, E., Morgenbesser, S.D., DePinho, R.A., Panayotatos, N., Cobb, M.H. & Yancopoulos, G.D. 1991. ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. Cell 65, 663-675.
14. Brunet, A. & Pouyssegur, J. 1997. Mammalian MAP kinase modules: how to transduce specific signals. Essays Biochem 32, 1-16.
15. Byrd, S.K., Bode, A.K. & Klug, G. A. 1989. Effects of exercise of varying duration on sarcoplasmic reticulum function. J Appl Physiol 66, 1383-1389.
16. Cavigelli, M., Dolfi, P., Claret, F.X. & Karin, M. 1995. Induction of c-fos expression through JNK-mediated TCP/Elk-1 phosphorylation. EMBO J 14, 5957-5964.
17. Chen, R.H., Sarnecki, C. & Blenis, J. 1992. Nuclear localization and regulation of ERK- and Rsk-encoded protein kinases. Mol Cell Biol 12, 915-927.
18. Chibalin, A.V., Yu, M., Ryder, J.W., Song, X.M., Galuska, D., Krook, A., Wallberg-Henriksson, H. & Zierath, J.R. 2000. Exercise-induced changes in expression and activity of proteins involved in insulin signal transduction in skeletal muscle: differential effects on insulin-receptor substrates 1 and 2. Proc Natl Acad Sci USA 97, 38-43.
19. Clarkson, P.M., Byrnes, W.C., McCormick, K.M., Turcotte, L.P. & White, J.S. 1986. Muscle soreness and serum creatine kinase activity following isometric, eccentric, and concentric exercise. Int J Sports Med 7, 152-155.
20. Cohen, P. 1997. The search for physiological substrates of MAP and SAP kinases in mammalian cells. Trends Cell Biol 7, 353-360.
21. Cooper, J.A. & Hunter, T. 1983. Identification and characterization of cellular targets for tyrosine protein kinases. J Biol Chem 258, 1108-1115.
22. Crespo, P., Xu, N., Simonds, W.F. & Gutkind, J.S. 1994. Rasdependent activation of MAP kinase pathway mediated by G-protein beta gamma subunits. Nature 369, 418-420.
23. Cuenda, A., Cohen, P., Buee-Scherrer, V. & Goedert, M. 1997. Activation of stress-activated protein kinase-3 (SAPK3) by cytokines and cellular stresses is mediated via SAPKK3 (MKK6); comparison of the specificities of SAPK3 and SAPK2 (RK/p38). EMBO J 16, 295-305.
24. Cuenda, A., Rouse, J., Doza, Y.N., Meier, R., Cohen, P., Gallagher, T.F., Young, P.R. & Lee, J.C. 1995. SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1. FEBS Lett 364, 229-233.
25. Deak, M., Clifton, A.D., Lucocq, L.M. & Alessi, D.R. 1998. Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. EMBO J 17, 4426-4441.
26. Downward, J. 1996. Control of ras activation. Cancer Surv 27, 87-100.
27. Fielding, R.A., Manfredi, T.J., Ding, W., Fiatarone, M.A., Evans, W.J. & Cannon, J.G. 1993. Acute phase response in exercise. III. Neutrophil and IL-1 beta accumulation in skeletal muscle. Am J Physiol 265, R166-R172.
28. Force, T. & Bonventre, J.V. 1998. Growth factors and mitogen-activated protein kinases. Hypertension 31, 152-161.
29. Friden, J., Sjostrom, M. & Ekblom, B. 1981. A morphological study of delayed muscle soreness. Experientia 37, 506-507.
30. Galcheva-Gargova, Z., Derijard, B., Wu, I.H. & Davis, R.J. 1994. An osmosensing signal transduction pathway in mammalian cells. Science 265, 806-808.
31. Ginty, D.D., Bonni, A. & Greenberg, M.E. 1994. Nerve growth factor activates a Ras-dependent protein kinase that stimulates c-fos transcription via phosphorylation of CREB. Cell 77, 713-725.
32. Goldberg, A.L., Etlinger, J.D., Goldspink, D.F. & Jablecki, C. 1975. Mechanism of work-induced hypertrophy of skeletal muscle. Med Sci Sports 7, 185-198.
33. Gonzalez, G.A. & Montminy, M.R. 1989. Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell 59, 675-680.
34. Goodyear, L.J., Chang, P.Y., Sherwood, D.J., Dufresne, S.D. & Moller, D.E. 1996. Effects of exercise and insulin on mitogen-activated protein kinase signaling pathways in rat skeletal muscle. Am J Physiol 271, E403-E408.
35. Gupta, S., Campbell, D., Derijard, B. & Davis, R.J. 1995. Transcription factor ATF2 regulation by the JNK signal transduction pathway. Science 267, 389-393.
36. Han, J., Jiang, Y., Li, Z., Kravchenko, V.V. & Ulevitch, R.J. 1997. Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation. Nature 386, 296-299.
37. Han, J., Lee, J.D., Bibbs, L. & Ulevitch, R.J. 1994. A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science 265, 808-811.
38. Hayashi, T., Hirshman, M.F., Dufresne, S.D. & Goodyear, L.J. 1999. Skeletal muscle contractile activity in vitro stimulates mitogen-activated protein kinase signaling. Am J Physiol 277, C701-C707.
39. Hazzalin, C.A., Cano, E., Cuenda, A., Barratt, M.J., Cohen, P. & Mahadevan, L.C. 1996. p38/RK is essential for stress-induced nuclear responses: JNK/SAPKs and c-Jun/ATF-2 phosphorylation are insufficient. Curr Biol 6, 1028-1031.
40. Henriksson, J. & Reitman, J.S. 1976. Quantitative measures of enzyme activities in type 1 and type II muscle fibres of man after training. Acta Physiol Scand 97, 392-397.
41. Hermansen, L. & Osnes, J.B. 1972. Blood and muscle pH after maximal exercise in man. J Appl Physiol 32, 304-308.
42. Hodge, C., Liao, J., Stofega, M., Guan, K., Carter-Su, C. & Schwartz, J. 1998. Growth hormone stimulates phosphorylation and activation of elk-1 and expression of c-fos, egr-1, and junB through activation of extracellular signal-regulated kinases 1 and 2. J Biol Chem 273, 31 327-31 336.
43. Holly, R.G., Barnett, J.G., Ashmore, C.R., Taylor, R.G. & Mole, P.A. 1980. Stretch-induced growth in chicken wing muscles: a new model of stretch hypertrophy. Am J Physiol 238, C62-C71.
44. Houmard, J.A., Egan, P.C., Neufer, P.D., Friedman, J.E., Wheeler, W.S., Israel, R.G. & Dohm, G.L. 1991. Elevated skeletal muscle glucose transporter levels in exercise-trained middle-aged men. Am J Physiol 261, E437-E443.
45. Houmard, J.A., Shaw, C.D., Hickey, M.S. & Tanner, C.J. 1999. Effect of short-term exercise training on insulin-stimulated PI 3- kinase activity in human skeletal muscle. Am J Physiol 277, E1055-E10560.
46. Hu, M.C., Wang, Y.P., Mikhail, A., Qiu, W.R. & Tan, T.H. 1999. Marine p38-delta mitogen-activated protein kinase, a developmentally regulated protein kinase that is activated by stress and proinflammatory cytokines. J Biol Chem 274, 7095-7102.
47. Hughes, V.A., Fiatarone, M.A., Fielding, R.A., Kahn, B.B., Ferrara, C.M., Shepherd, P., Fisher, E.C., Wolfe, R.R., Elahi, D. & Evans, W.J. 1993. Exercise increases muscle GLUT-4 levels and insulin action in subjects with impaired glucose tolerance. Am J Physiol 264, E855-E862.
48. Ichijo, H., Nishida, E., Irie, K., ten Dijke, P., Saitoh, M., Moriguchi, T., Takagi, M., Matsumoto, K., Miyazono, K. & Gotoh, Y. 1997. Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science 275, 90-94.
49. 2+ stimulation of CREB- dependent transcription and ERK nuclear translocation. Neuron 21, 869-883.
50. Jiang, Y., Gram, H., Zhao, M., New, L., Gu, J., Feng, L., Di Padova, P., Ulevitch, R.J. & Han, J. 1997. Characterization of the structure and function of the fourth member of p38 group mitogen-activated protein kinases, p38delta. J Biol Chem 272, 30 122-30 128.
51. Karin, M. 1995. The regulation of AP-1 activity by mitogen-activated protein kinases. J Biol Clem 270, 16 483-16 486.
52. Keesler, G.A., Bray, J., Hunt, J., Johnson, D.A., Gleason, T., Yao, Z., Wang, S.W., Parker, C., Yamane, H., Cole, C. & Lichenstein, H.S. 1998. Purification and activation of recombinant p38 isoforms alpha, beta, gamma, and delta. Protein Expr Purif 14, 221-228.
53. Kim, Y., Inoue, T., Nakajima, R. et al. 1995. Effects of endurance training on gene expression of insulin signal transduction pathway. Biochem Biopbys Res Commun 210, 766-773.
54. Komuro, I., Kudo, S., Yamazaki, T., Zou, Y., Shiojima, I. & Yazaki, Y. 1996. Mechanical stretch activates the stress-activated protein kinases in cardiac myocytes. FASEB J 10, 631-636.
55. Kraus, W.E., Bernard, T.S. & Williams, R.S. 1989. Interactions between sustained contractile activity and beta-adrenergic receptors in regulation of gene expression in skeletal muscles. Am J Physiol 256, C506-C514.
56. Krook, A., Björnholm, M., Galuska, D., Jiang, X.-J., Fahlman, R., Myers, M.G. Jr., Wallberg-Henriksson, H. & Zierath, J.R. 2000a. Characterization of signal transduction and glucose transport in skeletal muscle from type 2 diabetic patients. Diabetes 49, 284-292.
57. Krook, A., Widegren, U., Jiang, X.J., Henriksson, J., Wallberg-Henriksson, H., Alessi, D. & Zierath, J.R. 2000b. Effects of exercise on mitogen- and stress-activated kinase signal transduction in human skeletal muscle. Am J Physiol 279, R1716-R1721.
58. Kwok, R.P., Lundblad, J.R., Chrivia, J.C., Richards, J.P., Bachinger, H.P., Brennan, R.G., Roberts, S.G., Green, M.R. & Goodman, R.H. 1994. Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature 370, 223-226.
59. Kyriakis, J.M., Banerjee, P., Nikolakaki, E., Dai, T., Rubie, E.A., Ahmad, M.F., Avruch, J. & Woodgett, J.R. 1994. The stress-activated protein kinase subfamily of c-Jun kinases. Nature 369, 156-160.
60. Leppa, S., Saffrich, R., Ansorge, W. & Bohmann, D. 1998. Differential regulation of c-Jun by ERK and JNK during PC12 cell differentiation. EMBO J 17, 4404-4013.
61. Li, Z., Jiang, Y., Ulevitch, R.J. & Han, J. 1996. The primary structure of p38γ: a new member of p38 group of MAP kinase. Biochem Biophys Res Commun 228, 334-340.
62. Michel, J.B., Ordway, G.A., Richardson, J.A. & Williams, R.S. 1994. Biphasic induction of immediate early gene expression accompanies activity-dependent angiogenesis and myofiber remodeling of rabbit skeletal muscle. J Clin Invest 94, 277-285.
63. Murgia, M., Serrano, A.L., Calabria, E., Pallafacchina, G., Lomo, T. & Schiaffino, S. 2000. Ras is involved in nerve-activity-dependent regulation of muscle genes. Nat Cell Biol 2, 142-147.
64. Ogata, A., Chauhan, D., Teoh, G., Treon, S.P., Urashima, M., Schlossman, R.L. & Anderson, K.C. 1997. IL-6 triggers cell growth via the Ras-dependent mitogen-activated protein kinase cascade. J Immunol 159, 2212-2221.
65. O'Neill, C.A., Stebbins, C.L., Bonigut, S., Halliwell, B. & Longhurst, J.C. 1996. Production of hydroxyl radicals in contracting skeletal muscle of cats. J Appl Physiol 81, 1197-1206.
66. Osman, A.A., Pendergrass, M., Koval, J., Maezono, K., Cusi, K., Pratipanawatr, T. & Mandarino, L.J. 2000. Regulation of MAP kinase pathway activity in vivo in human skeletal muscle. Am J Physiol Endocrinol Metab 278, E992-E999.
67. Pages, G., Lenormand, P., L'Allemain, G., Chambard, J.C., Meloche, S. & Pouyssegur, J. 1993. Mitogen-activated protein kinases p42MAPK and p44MAPK are required for fibroblast proliferation. Proc Natl Acad Sci USA 90, 8319-8323.
68. Perrone, C.E., Fenwick-Smith, D. & Vandenburgh, H.H. 1995. Collagen and stretch modulate autocrine secretion of insulin-like growth factor-1 and insulin-like growth factor binding proteins from differentiated skeletal muscle cells. J Biol Chem 270, 2099-2106.
69. Ploug, T., van Deurs, B., Ai, H., Cushman, S.W. & Ralston, E. 1998. Analysis of GLUT4 distribution in whole skeletal muscle fibers: Identification of distinct storage compartments that are recruited by insulin and muscle contractions. J Cell Biol 142, 1429-1446.
70. Ray, L.B. & Sturgill, T.W. 1988. Insulin-stimulated microtubule-associated protein kinase is phosphorylated on tyrosine and threonine in vivo. Proc Natl Acad Sci USA 85, 3753-3777.
71. Ren, J.M., Semenkovich, C.F., Gulve, E.A., Gao, J. & Holloszy, J.O. 1994. Exercise induces rapid increases in GLUT4 expression, glucose transport capacity, and insulin-stimulated glycogen storage in muscle. J Biol Chem 269, 14 396-14 401.
72. Rouse, J., Cohen, P., Trigon, S., Morange, M., Alonso-Llamazares, A., Zamanillo, D., Hunt, T. & Nebreda, A.R. 1994. A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins. Cell 78, 1027-1037.
73. Ryder, J.W., Fahlman, R., Wallberg-Henriksson, H., Alessi, D.R., Krook, A. & Zierath, J.R. 2000. Effect of contraction on mitogen-activated protein kinase signal transduction in skeletal muscle. Involvement of the mitogen- and stress-activated protein kinase 1. J Biol Chem 275, 1457-1462.
74. Sanchez, I., Hughes, R.T., Mayer, B.J., Yee, K., Woodgett, J.R., Avruch, J., Kyriakis, J.M. & Zon, L.I. 1994. Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun. Nature 372, 794-798.
75. Schlaepfer, D.D., Hanks, S.K., Hunter, T. & van der Geer, P. 1994. Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase. Nature 372, 786-791.
76. Schonwasser, D.C., Marais, R.M., Marshall, C.J. & Parker, P.J. 1998. Activation of the mitogen-activated protein kinase/ extracellular signal-regulated kinase pathway by conventional, novel, and atypical protein kinase C isotypes. Mol Cell Biol 18, 790-798.
77. Seger, R., Ahn, N.G., Posada, J., Munar, E.S., Jensen, A.M., Cooper, J.A., Cobb, M.H. & Krebs, E.G. 1992. Purification and characterization of mitogen-activated protein kinase activator (s) from epidermal growth factor-stimulated A431 cells. J Biol Chem 267, 14 373-14 381.
78. Seko, Y., Tobe, K., Ueki, K., Kadowaki, T. & Yazaki, Y. 1996. Hypoxia and hypoxia/reoxygenation activate Raf-1, mitogen-activated protein kinase kinase, mitogen-activated protein kinases, and S6 kinase in cultured rat cardiac myocytes. Circ Res 78, 82-90.
79. Sheng, M., Thompson, M.A. & Greenberg, M.E. 1991. CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases. Science 252, 1427-1430.
80. Sherwood, D.J., Dufresne, S.D., Markuns, J.F., Cheatham, B., Moller, D.E., Aronson, D. & Goodyear, L.J. 1999. Differential regulation of MAP kinase, p70 (S6K), and Akt by contraction and insulin in rat skeletal muscle. Am J Physiol 276, E870-E878.
81. Shoubridge, E.A., Challiss, R.A., Hayes, D.J. & Radda, G.K. 1985. Biochemical adaptation in the skeletal muscle of rats depleted of creatine with the substrate analogue beta-guanidinopropionic acid. Biochem J 232, 125-131.
82. Skolnik, E.Y., Batzer, A., Li, N., Lee, C.H., Lowenstein, E., Mohammadi, M., Margolis, B. & Schlessinger, J. 1993. The function of GRB2 in linking the insulin receptor to Ras signaling pathways. Science 260, 1953-1955.
83. Sreter, F.A., Lopez, J.R., Alamo, L., Mabuchi, K. & Gergely, J. 1987. Changes in intracellular ionized Ca concentration associated with muscle fiber type transformation. Am J Physiol 253, C296-C300.
84. Stancato, L.F., Sakatsume, M., David, M., Dent, P., Dong, F., Petricoin, E.F., Krolewski, J.J., Silvennoinen, O., Saharinen, P., Pierce, J., Marshall, C.J., Sturgill, T., Finbloom, D.S. & Lamer, A.C. 1997. Beta interferon and oncostatin M activate Raf-1 and mitogen-activated protein kinase through a JAK1-dependent pathway. Mol Cell Biol 17, 3833-3840.
85. Stebbins, C.L., Carretero, O.A., Mindroiu, T. & Longhurst, J.C. 1990. Bradykinin release from contracting skeletal muscle of the cat. J Appl Physiol 69, 1225-1230.
86. Stugill, T.W., Ray, L.B., Erikson, E. & Maller, J.L. 1988. Insulin-stimulated MAP-2 kinase phosphorylates and activates ribosomal protein S6 kinase II. Nature 334, 715-718.
87. Terrados, N., Jansson, E., Sylven, C. & Kaijser, L. 1990. Is hypoxia a stimulus for synthesis of oxidative enzymes and myoglobin? J Appl Physiol 68, 2369-2372.
88. Thomson, S., Clayton, A.L., Hazzalin, C.A., Rose, S., Barratt, M.J. & Mahadevan, L.C. 1999. The nucleosomal response associated with immediate-early gene induction is mediated via alternative MAP kinase cascades: MSK1 as a potential histone H3/HMG-14 kinase. EMBO J 18, 4779-4793.
89. Wang, P.H., Schaaf, G.J., Chen, W.H., Feng, J., Prins, B.A., Levin, E.R. & Bahl, J.J. 1998. IGF I induction of p53 requires activation of MAP kinase in cardiac muscle cells. Biochem Biophys Res Commun 245, 912-917.
90. Widegren, U., Jiang, X.J., Krook, A., Chibalin, A.V., Bjornholm, M., Tally, M., Roth, R.A., Henriksson, J., Wallberg-Henriksson, H. & Zierath, J.R. 1998. Divergent effects of exercise on metabolic and mitogenic signaling pathways in human skeletal muscle. FASEB J 12, 1379-1389.
91. Widegren, U., Wretman, C., Lionikas, A., Hedin, G. & Henriksson, J. 2000. Influence of exercise intensity on ERK/MAP kinase signalling in human skeletal muscle. Pflugers Arch Eur J Physiol 441, 317-322.
92. Widmann, C., Gibson, S., Jarpe, M.B. & Johnson, G.L. 1999. Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev 79, 143-180.
93. Winston, L.A. & Hunter, T. 1996. Intracellular signalling: putting JAKs on the kinase MAP. Curr Biol 6, 668-671.
94. Wojtaszewski, J.F., Lynge, J., Jakobsen, A.B., Goodyear, L.J. & Richter, E.A. 1999. Differential regulation of MAP kinase by contraction and insullin in skeletal muscle: metabolic implications. Am J Physiol 277, E724-E732.
95. Wretman, C., Widegren, U., Lionikas, A., Westerblad, H. & Henriksson, J. 2000. Differential activation of mitogen-activated protein kinase signalling pathways by isometric contractions in isolated slow- and fast-twitch rat skeletal muscle. Acta Physiol Scand 170, 45-49.
96. Xing, J., Ginty, D.D. & Greenberg, M.E. 1996. Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase. Science 273, 959-963.
97. Yamazaki, T., Komuro, I., Kudoh, S., Zou, Y., Shiojima, I., Mizuno, T., Takano, H., Hiroi, Y., Ueki, K., Tobe, K. et al. 1995. Mechanical stress activates protein kinase cascade of phosphorylation in neonatal rat cardiac myocytes. J Clin Invest 96, 438-446.
98. Yamazaki, T., Tobe, K., Hoh, E., Maemura, K., Kaida, T., Komuro, I., Tamemoto, H., Kadowaki, T., Nagai, R. & Yazaki, Y. 1993. Mechanical loading activates mitogen-activated protein kinase and S6 peptide kinase in cultured rat cardiac myocytes. J Biol Chem 268, 12069-12076.
99. Yu, M., Blomstrand, E., Chibalin, A.V., Wallberg-Henriksson, H., Zierath, J.R. & Krook, A. 2001. Exercise-associated difference in an array of proteins involved in signal transduction and glucose transport. J Appl Physiol 90, 29-34.
100. Zhang, S., Han, J., Sells, M.A., Chernoff, J., Knaus, U.G., Ulevitch, R.J. & Bokoch, G.M. 1995. Rho family GTPases regulate p38 mitogen-activated protein kinase through the downstream mediator Pak1. J Biol Chem 270, 23934-23936.
101. Zhao, Y., Bjorbaek, C. & Moller, D.E. 1996. Regulation and interaction of pp90 (rsk) isoforms with mitogen-activated protein kinases. J Biol Chem 271, 29773-29779.
102. Zheng, C.F. & Guan, K.L. 1993. Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases. J Biol Chem 268, 23933-23939.