Bennett, A. M., Tonks, N. K. (November 1997) Regulation of distinct stages of skeletal muscle differentiation by mitogen-activated protein kinases. Science, 278 (5341). pp. 1288-1291. ISSN 0036-8075
Abstract
The signal transduction pathway or pathways linking extracellular signals to myogenesis are poorly defined. Upon mitogen withdrawal from C2C12 myoblasts, the mitogen-activated protein kinase (MAPK) p42Erk2 is inactivated concomitant with up-regulation of muscle-specific genes, Overexpression of MAPK phosphatase-1 (MKP-1) inhibited p42Erk2 activity and was sufficient to relieve the inhibitory effects of mitogens on muscle-specific gene expression. Later during myogenesis, endogenous expression of MKP-1 decreased. MKP-1 overexpression during differentiation prevented myotube formation despite appropriate expression of myosin heavy chain, This indicates that muscle-specific gene expression is necessary but not sufficient to commit differentiated myocytes to myotubes and suggests a function for the MAPKs during the early and late stages of skeletal muscle differentiation.
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