Effects of exercise on mitogen- and stress-activated kinase signal transduction in human skeletal muscle

Exercise/contraction is a powerful stimulator of mitogen-activated protein (MAP) kinase cascades in skeletal muscle. Little is known regarding the phy siological activation of enzymes downstream of MAP kinase. We investigated whether acute exercise results in activation of mitogen- and stress-activat ed kinases (MSK) 1 and 2, p90 ribosomal S6 kinase (p90rsk), and MAP kinase- activated protein kinase 2 (MAPKAPK2). Muscle biopsies were obtained from h ealthy volunteers before, during, and after 60 min one-leg cycle ergometry, from exercising and resting legs. MSK1 and MSK2 activities were increased 400-500% and 200-300%, respectively, in exercised muscle (P < 0.05 vs. rest ). A dramatic increase in activity of p90rsk (MAPKAPK1) (>2,500%), and to a lesser extent MAPKAP2 (300%), was noted with exercise (P < 0.05 vs. rest). MSK1, MSK2, p90rsk, and MAPKAP2 activities were sustained throughout exerc ise. Exercise-induced activation of these enzymes was limited to working mu scle, indicating that local rather than systemic factors activate these sig naling cascades. Thus physical exercise leads to activation of multiple enz ymes downstream of MAP kinase.