PI3K p110α and p110Β have differential effects on Akt activation and protection against oxidative stress-induced apoptosis in myoblasts

R. W. Matheny, M. L. Adamo

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Catalytic subunits of phosphoinositide-3-kinase (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 insulin-like growth factor-I (IGF-I)-stimulated Akt activity and prevented IGF-I-mediated survival in H 2O2-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 extracellular signal-regulated kinase (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 insulin-like growth factor-I receptor (IGF-IR) endocytosis. We also report that IGF-I protects myoblasts from H 2O2-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.

Original languageEnglish (US)
Pages (from-to)677-688
Number of pages12
JournalCell Death and Differentiation
Volume17
Issue number4
DOIs
StatePublished - Apr 2010

Keywords

  • Apoptosis
  • Insulin-like growth factor-I
  • Myoblast
  • Phosphoinositide-3-kinase
  • Protein kinase B/Akt

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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