Enhanced Akt phosphorylation and myogenic differentiation in PI3K p110β-deficient myoblasts is mediated by PI3K p110α and mTORC2

Abstract

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.

Keywords::

• PI3K
• Akt
• mTOR
• myoblast
• myogenesis

Acknowledgements

The authors thank Dr Jonathan Backer of the Albert Einstein College of Medicine, Bronx, NY, for the generous gift of plasmids encoding wild-type p110α.

Declaration of interest : This work was supported by an appointment to the Postgraduate Research Participation Program at the US Army Research Institute of Environmental Medicine administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and USAMRMC (CML). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Army or the Department of Defense. Citations of commercial organizations and trade names in this report do not constitute an official Department of the Army endorsement or approval of the products or services of these organizations.