Keren Aviad, Tamir Yael, Bengal Eyal
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.
Mol Cell Endocrinol. 2006 Jun 27;252(1-2):224-30. doi: 10.1016/j.mce.2006.03.017. Epub 2006 Apr 27.
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.
骨骼肌发育受细胞外生长因子调控，这些因子将 largely unknown 信号传入细胞，影响肌肉转录程序。在成肌细胞系分化过程中激活的一条细胞内信号通路是 p38 丝裂原活化蛋白激酶（MAPK）。通过改变成肌细胞中 p38 的活性，该通路被证明对肌肉特异性基因的表达至关重要。P38 影响 MyoD 和 MEF2 家族转录因子的活性，并参与特定肌肉调节区域的染色质重塑。P38 与成肌转录因子协同作用，激活一部分晚期转录基因，从而促进分化过程中基因的时序表达。最近对小鼠和非洲爪蟾胚胎的发育研究，证实并进一步扩展了 p38 在肌生成中的重要作用。有证据支持 p38 信号在小鼠体节发育过程中激活 MEF2 转录因子方面的关键作用。在非洲爪蟾中，p38 信号被证明是 Myf5 早期表达以及几个肌肉结构基因表达所必需的。新出现的数据表明 p38 参与了肌生成程序的多个阶段。
