Phosphatidylinositol 3-kinase stimulates muscle differentiation by activating p38 mitogen-activated protein kinase
Phosphatidylinositol 3-kinase stimulates muscle differentiation by activating p38 mitogen-activated protein kinase
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DOI：
10.1006/bbrc.2000.3486
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发表时间：
2000-09-24
影响因子：
3.1
通讯作者：
Kim, SS
中科院分区：
文献类型：
--
作者：
Chun, YK;Kim, J;Kim, SS
磷脂酰肌醇3-激酶（PI3-kinase）和p38丝裂原活化蛋白激酶（p38 MAPK）的激活是肌肉分化所必需的。然而，目前尚不清楚这两种激酶的信号是否在这一过程中相互作用。在这项工作中，我们用H9c2心肌母细胞研究了这一点。p38 mapk特异性抑制剂SB203580阻断肌肉分化，并以浓度依赖的方式抑制肌原蛋白和肌球蛋白重链的表达。与此一致的是，野生型p38 MAPK （Ha-p38）或组成型活性MAPK激酶6（MKK6(glu)）的表达促进了向多核肌管分化的速度。LY294002，一种pi3激酶抑制剂，不仅以剂量依赖的方式抑制肌肉分化，还抑制p38 MAPK的激活。此外，pi3激酶（p110*）的组成活性形式的表达增强了肌管的形成和p38 MAPK。而pi3激酶的显性阴性形式（Delta p85）的表达则减弱了这些反应。此外，SB203580抑制表达p110*的H9c2细胞的分化。有趣的是，LY294002也抑制了表达Ha-p38或MKK6（glu）的H9c2细胞的分化。然而，SB203580不影响pi3激酶的活性，这表明pi3激酶对p38 MAPK的肌原性信号是单向的。综上所述，我们得出结论，pi3激酶激活p38 MAPK，进而刺激肌肉分化，但p38 MAPK在这一过程中不能替代pi3激酶。(C) 2000年学术出版社。
The activation of both phosphatidylinositol 3-kinase (PI3-kinase) and p38 mitogen-activated protein kinase (p38 MAPK) is required for muscle differentiation. However, it is not known whether the signals from these two kinases interact during this process. In this work, we have investigated this using H9c2 cardiac myoblasts. The p38 MAPK-specific inhibitor SB203580 blocked muscle differentiation and suppressed the expression of myogenin and myosin heavy chain in a concentration-dependent manner. Consistent with this, expression of a wild-type p38 MAPK (Ha-p38) or a constitutively active MAPK kinase 6 (MKK6(glu)) promoted the rate of differentiation into multinucleated myotubes. LY294002, a PI3-kinase inhibitor, suppressed in a dose-dependent manner not only muscle differentiation but also activation of p38 MAPK. In addition, expression of a constitutively active form of PI3-kinase (p110*) enhanced myotube formation and p38 MAPK. activation, while expression of a dominant negative form of PI3-kinase (Delta p85) attenuated these responses. Furthermore, SB203580 suppressed differentiation of H9c2 cells expressing p110*. Interestingly, LY294002 also suppressed differentiation of H9c2 cells expressing Ha-p38 or MKK6(glu). However, SB203580 did not affect PI3-kinase activity, suggesting that PI3-kinase myogenic signaling to p38 MAPK is unidirectional. Taken together, we concluded that PI3-kinase activates p38 MAPK, which in turn stimulates muscle differentiation, but that p38 MAPK does not substitute for PI3-kinase in this process. (C) 2000 Academic Press.