Matheny Ronald W, Lynch Christine M, Leandry Luis A
Military Performance Division, US Army Research Institute of Environmental Medicine, 15 Kansas Street, Building 42, Natick, MA 01760, USA.
Growth Factors. 2012 Dec;30(6):367-84. doi: 10.3109/08977194.2012.734507. Epub 2012 Nov 9.
Phosphoinositide 3-kinase (PI3K) is a principal regulator of Akt activation and myogenesis; however, the function of PI3K p110β in these processes is not well defined. To address this, we investigated the role of p110β in Akt activation and skeletal muscle cell differentiation. We found that Akt phosphorylation was enhanced in p110β-deficient myoblasts in response to Insulin-like Growth Factor-I (IGF-I), epidermal growth factor, or p110α overexpression, as compared to p110β-sufficient cells. This effect was associated with increased mammalian target of rapamycin complex 2 activation, even in myoblasts deficient in mSin1 and rictor. Conversely, in response to the G-protein-coupled receptor agonist lysophosphatidic acid, Akt phosphorylation was attenuated in p110β-deficient myoblasts. Loss of p110β also enhanced the expression of myogenic markers at the myoblast stage and during the first 48 h of differentiation. These data demonstrate that reductions in p110β are associated with agonist-specific Akt hyperactivation and accelerated myogenesis, thus revealing a negative role for p110β in Akt activation and during myoblast differentiation.
磷脂酰肌醇3激酶（PI3K）是Akt激活和肌生成的主要调节因子；然而，PI3K p110β在这些过程中的功能尚未明确界定。为了解决这个问题，我们研究了p110β在Akt激活和骨骼肌细胞分化中的作用。我们发现，与p110β充足的细胞相比，在胰岛素样生长因子-I（IGF-I）、表皮生长因子或p110α过表达刺激下，p110β缺陷的成肌细胞中Akt磷酸化增强。即使在缺乏mSin1和rictor的成肌细胞中，这种效应也与雷帕霉素复合物2的哺乳动物靶标激活增加有关。相反，在G蛋白偶联受体激动剂溶血磷脂酸刺激下，p110β缺陷的成肌细胞中Akt磷酸化减弱。p110β的缺失还增强了成肌细胞阶段以及分化最初48小时期间肌生成标志物的表达。这些数据表明，p110β的减少与激动剂特异性Akt过度激活和加速肌生成有关，从而揭示了p110β在Akt激活和成肌细胞分化过程中的负性作用。
