The p38 MAPK signaling pathway: A major regulator of skeletal muscle development

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Mol Cell Endocrinol. 2006 Apr

The p38 MAPK signaling pathway: A major regulator of skeletal muscle

development.

Keren A, Tamir Y, Bengal E.

Department of Biochemistry, Rappaport Institute for Research in the

Medical Sciences, Faculty of Medicine, Technion-Israel Institute of

Technology, P.O. Box 9649, Haifa 31096, Israel.

Skeletal muscle development is regulated by extracellular growth

factors that transmit largely unknown signals into the cell affecting

the muscle-transcription program. One intracellular signaling pathway

activated during the differentiation of myogenic cell lines is p38

mitogen-activated protein kinase (MAPK). As a result of modifying the

activity of p38 in myoblasts, the pathway proved essential for the

expression of muscle-specific genes. P38 affects the activities of

transcription factors from the MyoD and MEF2 families and

participates in the remodeling of chromatin at specific muscle-

regulatory regions. P38 cooperates with the myogenic transcription

factors in the activation of a subset of late-transcribed genes,

hence contributing to the temporal expression of genes during

differentiation. Recent developmental studies with mouse and Xenopus

embryos, substantiated and further extended the essential role of p38

in myogenesis. Evidence exists supporting the crucial role for p38

signaling in activating MEF2 transcription factors during somite

development in mice. In Xenopus, p38 signaling was shown to be needed

for the early expression of Myf5 and for the expression of several

muscle structural genes. The emerging data indicate that p38

participates in several stages of the myogenic program.