• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >p38 and Extracellular Signal-Regulated Kinases Regulate the Myogenic Program at Multiple Steps
【24h】

p38 and Extracellular Signal-Regulated Kinases Regulate the Myogenic Program at Multiple Steps

机译：p38和细胞外信号调节激酶在多个步骤调节肌源性程序。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The extracellular signals which regulate the myogenic program are transduced to the nucleus by mitogen-activated protein kinases (MAPKs). We have investigated the role of two MAPKs, p38 and extracellular signal-regulated kinase (ERK), whose activities undergo significant changes during muscle differentiation. p38 is rapidly activated in myocytes induced to differentiate. This activation differs from those triggered by stress and cytokines, because it is not linked to Jun–N-terminal kinase stimulation and is maintained during the whole process of myotube formation. Moreover, p38 activation is independent of a parallel promyogenic pathway stimulated by insulin-like growth factor 1. Inhibition of p38 prevents the differentiation program in myogenic cell lines and human primary myocytes. Conversely, deliberate activation of endogenous p38 stimulates muscle differentiation even in the presence of antimyogenic cues. Much evidence indicates that p38 is an activator of MyoD: (i) p38 kinase activity is required for the expression of MyoD-responsive genes, (ii) enforced induction of p38 stimulates the transcriptional activity of a Gal4-MyoD fusion protein and allows efficient activation of chromatin-integrated reporters by MyoD, and (iii) MyoD-dependent myogenic conversion is reduced in mouse embryonic fibroblasts derived from p38α?/? embryos. Activation of p38 also enhances the transcriptional activities of myocyte enhancer binding factor 2A (MEF2A) and MEF2C by direct phosphorylation. With MEF2C, selective phosphorylation of one residue (Thr293) is a tissue-specific activating signal in differentiating myocytes. Finally, ERK shows a biphasic activation profile, with peaks of activity in undifferentiated myoblasts and postmitotic myotubes. Importantly, activation of ERK is inhibitory toward myogenic transcription in myoblasts but contributes to the activation of myogenic transcription and regulates postmitotic responses (i.e., hypertrophic growth) in myotubes.
机译：调节肌原性程序的细胞外信号通过丝裂原活化的蛋白激酶（MAPK）转导至细胞核。我们研究了两个MAPK，p38和细胞外信号调节激酶（ERK）的作用，它们的活性在肌肉分化过程中发生了显着变化。 p38在诱导分化的心肌细胞中迅速激活。这种激活不同于由压力和细胞因子触发的激活，因为它与Jun-N端激酶刺激无关，并且在肌管形成的整个过程中都得到维持。此外，p38的激活独立于胰岛素样生长因子1刺激的平行早生途径。抑制p38可以阻止成肌细胞系和人原代心肌细胞中的分化程序。相反，内源性p38的故意激活即使在存在抗肌源性线索的情况下也能刺激肌肉分化。许多证据表明p38是MyoD的激活剂：（i）表达MyoD响应基因需要p38激酶活性;（ii）强制诱导p38可以刺激Gal4-MyoD融合蛋白的转录活性并允许有效激活（iii）在源自p38α？/？胚胎的小鼠胚胎成纤维细胞中，MyoD依赖的成肌转化减少。 p38的激活还通过直接磷酸化增强了肌细胞增强剂结合因子2A（MEF2A）和MEF2C的转录活性。使用MEF2C，一个残基的选择性磷酸化（Thr293）是分化心肌细胞中的一种组织特异性激活信号。最后，ERK显示出双相激活曲线，在未分化的成肌细胞和有丝分裂后的肌管中具有峰值活性。重要的是，ERK的激活抑制成肌细胞中的肌原性转录，但是有助于肌原性转录的激活并调节肌管中的有丝分裂后反应（即肥大性生长）。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号