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Research Article

PI3K p110α and p110β have differential effects on Akt activation and protection against oxidative stress-induced apoptosis in myoblasts



Abstract

Catalytic subunits of PI3K play a critical role in growth factor signaling and survival by phosphorylating inositol lipids. We found that PI3K Class IA p110α and p110β have distinct functions in myoblasts. Inhibition of p110α reduced IGF-I-stimulated Akt activity and prevented IGF-I-mediated survival in H2O2-treated cells; in contrast, siRNA knockdown of p110β increased IGF-I-stimulated Akt activity. However, inhibition of p110β catalytic activity did not increase IGF-I-stimulated Akt activity, suggesting a role for p110β protein interactions rather than decreased generation of phosphoinositides in this effect. Increased Akt activity in p110β-deficient myoblasts was associated with diminished ERK activation as well as ERK-dependent IRS-1 636/639 phosphorylation, findings we show to be independent of p110β catalytic function, but associated with IGF-IR endocytosis. We also report that IGF-I protects myoblasts from H2O2-induced apoptosis through a mechanism that requires p110α, but may be independent of Akt or ERK under conditions of Akt and ERK inhibition. These observations suggest that both p110α and p110β are essential for growth and metabolism in myoblasts. Overall, our results provide new evidence for the roles of p110 isoforms in promoting cellular proliferation and homeostasis, IGF-IR internalization, and in opposing apoptosis.


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