Divergent effects of exercise on metabolic and mitogenic signaling pathways in human skeletal muscle

The molecular signaling mechanisms by which muscle contractions lead to changes in glucose metabolism and gene expression remain largely undefined. We assessed whether exercise activates MAP kinase proteins (ERK1/2, SEK1, and p38 MAP kinase) as well as Akt and PYK2 in skeletal muscle from healthy volunteers obtained during and after one‐leg cycle ergometry at ∼70% VO 2max . Exercise led to a marked increase in ERK1/2 phosphorylation, which rapidly decreased to resting levels upon recovery. Exercise increased phosphorylation of SEK1 and p38 MAP kinase to a lesser extent than ERK1/2. In contrast to ERK1/2, p38 MAP kinase phosphorylation was increased in nonexercised muscle upon cessation of exercise. Phosphorylation of the transcription factor CREB was increased in nonexercised muscle upon cessation of exercise. Exercise did not activate Akt or increase tyrosine phosphorylation of PYK2. Thus, exercise has divergent effects on parallel MAP kinase pathways, of which only p38 demonstrated a systemic response. However, our data do not support a role of Akt or PYK2 in exercise/contraction‐induced signaling in human skeletal. Activation of the different MAP kinase pathways byphysical exercise appears to be important in the regulation of transcriptional events in skeletal muscle.—Widegren, U., Jiang, X.‐J., Krook, A., Chibalin, A. V., Bjo¨rnholm, M., Tally, M., Roth, R. A., Henriksson, J., Wallberg‐ Henriksson, H., Zierath, J. R. Divergent effects of exercise on metabolic and mitogenic signaling pathways in human skeletal muscle. FASEB J. 12, 1379– 1389 (1998)