Contractile activity stimulates the c-Jun NH2-terminal kinase pathway in rat skeletal muscle.
Contractile activity plays a critical role in the regulation of gene transcription in skeletal muscle, which in turn determines muscle functional capabilities. However, little is known about the molecular signaling mechanisms that convert contractile activity into gene regulatory responses in skeletal muscle. In the current study we determined the effects of contractile activity in vivo on the c-Jun NH2-terminal kinase (JNK) pathway, a signaling cascade that has been implicated in the regulation of transcription. Electrical stimulation of the sciatic nerve to produce contractions in anaesthetized rats increased JNK activity by up to 7-fold above basal. Maximal enzyme activity occurred at 15 min of contraction and remained elevated at 60 min of contraction. The upstream activators of JNK, the mitogen-activated protein kinase kinase 4 and the mitogen-activated protein kinase kinase kinase 1 followed a similar time course of activation in response to contractile activity. In contrast, contraction induced a rapid and transient activation of the extracellular-regulated kinase pathway, indicating that the regulation of JNK signaling is distinct from that of extracellular-regulated kinase. The activation of the JNK signaling cascade was temporally associated with an increased expression of c-jun mRNA. These results demonstrate that contractile activity regulates JNK activity in skeletal muscle and suggest that activation of JNK may regulate contraction-induced gene expression in skeletal muscle.
Aronson
D
D
Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA.
Dufresne
S D
SD
Goodyear
L J
LJ
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000201:enzymology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases