Role of Phosphatidylinositol 3,4,5-Trisphosphate (PIP3) 5-Phosphatase Skeletal Muscle- and Kidney-enriched Inositol Polyphosphate Phosphatase (SKIP) in Myoblast Differentiation*
Role of Phosphatidylinositol 3,4,5-Trisphosphate (PIP3) 5-Phosphatase Skeletal Muscle- and Kidney-enriched Inositol Polyphosphate Phosphatase (SKIP) in Myoblast Differentiation*
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磷脂酰肌醇 3,4,5-三磷酸 (PIP3) 5-磷酸酶 骨骼肌和肾脏富含肌醇多磷酸磷酸酶 (SKIP) 在成肌细胞分化中的作用*
DOI：
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发表时间：
2012
影响因子：
4.8
通讯作者：
T. Takenawa
中科院分区：
文献类型：
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作者：
T. Ijuin;T. Takenawa
背景：Skip是一种PIP35-磷酸酶，在骨骼肌中负向调节胰岛素信号。结果：SKIP过表达抑制了IGF-II的表达和成肌细胞的分化。结论：SKIP通过抑制IGF-II-Akt-mTor信号通路负向调节肌细胞分化。意义：Skip是肌肉细胞分化的关键调节因子。胰岛素样生长因子(IGF)对骨骼肌的发育、再生和肥大是必不可少的。IGF-II通过磷脂酰肌醇3-激酶(PI-3-K)、Akt和mTOR信号通路促进成肌细胞分化。在这里，我们报告了骨骼肌和肾脏富含肌醇多磷酸酶(SKIP)通过抑制IGF-II的产生和IGF-II-Akt-mTor信号通路的减弱来负向调节肌肉发生。我们还证明，在C2C12细胞中，在分化过程中显著升高的Skip表达受MyoD的控制。Skip在转录水平上抑制IGF-II的表达。这些结果表明，Skip对MyoD介导的肌肉分化具有调节作用。沉默SKIP可促进IGF-II转录和成肌细胞分化。此外，与对照C2C12细胞相比，Skip基因的敲除导致了较厚的肌管有更多的核。综上所述，这些数据表明，在肌肉发生过程中，Skip控制着IGF-II-PI3-Kinase-Akt-mTor自动调节环。我们的发现确定SKIP是肌肉细胞分化的关键调节因子。
Background: SKIP is a PIP3 5-phosphatase that negatively regulates insulin signaling in the skeletal muscle. Results: Overexpression of SKIP inhibited IGF-II expression and the myoblast cell differentiation. Conclusion: SKIP negatively regulated muscle cell differentiation through the attenuation of IGF-II-Akt-mTOR signaling pathway. Significance: SKIP is a key regulator if muscle cell differentiation. Insulin-like growth factors (IGFs) are essential for the development, regeneration, and hypertrophy of skeletal muscles. IGF-II promotes myoblast differentiation through phosphatidylinositol 3-kinase (PI 3-kinase), Akt, and mTOR signaling. Here, we report that skeletal muscle- and kidney-enriched inositol polyphosphate phosphatase (SKIP) negatively regulates myogenesis through inhibition of IGF-II production and attenuation of the IGF-II-Akt-mTOR signaling pathway. We also demonstrate that SKIP expression, which was markedly elevated during differentiation, was controlled by MyoD in C2C12 cells. Expression of SKIP inhibited IGF-II at the transcription level. These results indicate that SKIP regulates MyoD-mediated muscle differentiation. Silencing of SKIP increased IGF-II transcription and myoblast differentiation. Furthermore, knockdown of SKIP resulted in thick myotubes with a larger number of nuclei than that in control C2C12 cells. Taken together, these data indicate that SKIP controls the IGF-II-PI 3-kinase-Akt-mTOR auto-regulation loop during myogenesis. Our findings identify SKIP as a key regulator of muscle cell differentiation.
DOI：
10.1073/pnas.95.24.14179
发表时间：
1998-11-24
影响因子：
11.1
作者：
Jiang, BH;Zheng, JZ;Vogt, PK
通讯作者：
Vogt, PK
影响因子：
16
作者：
Bergstrom, DA;Penn, BH;Tapscott, SJ
通讯作者：
Tapscott, SJ