Suppression of c-Src activity stimulates muscle differentiation via p38 MAPK activation
Suppression of c-Src activity stimulates muscle differentiation via p38 MAPK activation
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DOI：
10.1016/j.abb.2007.06.004
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发表时间：
2007-09-01
影响因子：
3.9
通讯作者：
Kim, Sung Soo
中科院分区：
文献类型：
--
作者：
Lim, Min Jin;Seo, Yong Hak;Kim, Sung Soo
c-Src在肌肉分化中的作用一直存在争议。在这里，我们用H9c2和C2C12细胞系研究了c-Src是否正向或负向调节肌肉分化。用PP I和SU6656 （Src家族激酶的药理学抑制剂）治疗c-Src，或通过表达显性阴性c-Src，均可诱导增殖培养基（PM）中的肌肉分化。在分化培养基（DM）中的分化细胞中，c-Src活性逐渐降低，诱导分化后3天达到基础水平。c-Src的抑制抑制了Raf/MEK/ERK通路，但激活了p38 MAPK。抑制p38 MAPK不影响PM中c-Src的活性。然而，在c-Src抑制的细胞中，无论是PM还是DM，它都重新激活了Raf/MEK/ERK通路。同时抑制c-Src和p38 MAPK活性阻断了两种培养基中的肌肉分化。总之，c-Src活性的抑制通过单向激活p38 MAPK来刺激肌肉分化。(c) 2007爱思唯尔公司版权所有。
Role of c-Src in muscle differentiation has been controversial. Here, we investigated if c-Src positively or negatively regulates muscle differentiation, using H9c2 and C2C12 cell lines. Inhibition of c-Src by treatment with PP I and SU6656, pharmacologic inhibitors of Src family kinases, or by expression of a dominant negative c-Src, all induced muscle differentiation in proliferation medium (PM). In differentiating cells in differentiation medium (DM), c-Src activity gradually decreased and reached basal level 3 days after induction of differentiation. Inhibition of c-Src suppressed Raf/MEK/ERK pathway but activated p38 MAPK. Inhibition of p38 MAPK did not affect c-Src activity in PM. However, it reactivated Raf/MEK/ERK pathway in c-Src-inhibited cells regardless of PM or DM. Concomitant inhibition of c-Src and p38 MAPK activities blocked muscle differentiation in both media. In conclusion, suppression of c-Src activity stimulates muscle differentiation by activating p38 MAPK uni-directionally. (c) 2007 Elsevier Inc. All rights reserved.