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PI3K p110 alpha and p110 beta have differential effects on Akt activation and protection against oxidative

R W Matheny1, M L Adamo

  • 1Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.

Cell Death and Differentiation
|October 17, 2009
PubMed

Insights

Phosphoinositide-3-kinase (PI3K) Class IA p110 alpha and p110 beta subunits have distinct roles in myoblast growth and survival. P110 alpha is vital for insulin-like growth factor-I (IGF-I)-mediated survival, while p110 beta influences IGF-I signaling through protein interactions.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Phosphoinositide-3-kinase (PI3K) catalytic subunits, specifically p110 alpha and p110 beta, are crucial for cellular processes.
  • These subunits mediate growth factor signaling and cellular survival by phosphorylating inositol lipids.

Purpose of the Study:

  • To elucidate the distinct functions of PI3K Class IA p110 alpha and p110 beta isoforms in myoblasts.
  • To investigate their roles in insulin-like growth factor-I (IGF-I) signaling, Akt and extracellular signal-regulated kinase (ERK) activation, and cellular survival.

Main Methods:

  • Utilized pharmacological inhibition and small interfering RNA (siRNA) knockdown to study p110 alpha and p110 beta functions.
  • Assessed Akt and ERK activation, insulin-like growth factor-I receptor (IGF-IR) endocytosis, and apoptosis in response to IGF-I and hydrogen peroxide (H2O2).

Main Results:

  • Inhibition of p110 alpha reduced IGF-I-stimulated Akt activity and IGF-I-mediated survival.
  • siRNA knockdown of p110 beta increased IGF-I-stimulated Akt activity, but inhibition of its catalytic activity did not, suggesting a role for protein interactions.
  • P110 beta deficiency led to diminished ERK activation, altered IGF-IR endocytosis, and was independent of p110 beta catalytic function.
  • IGF-I-mediated protection from apoptosis involved p110 alpha and was potentially independent of Akt or ERK under specific inhibition conditions.

Conclusions:

  • PI3K p110 alpha and p110 beta isoforms play essential, distinct roles in myoblast growth, metabolism, and homeostasis.
  • Findings highlight the importance of p110 isoforms in IGF-IR internalization and apoptosis regulation.
  • The study provides novel insights into the differential functions of PI3K catalytic subunits in cellular signaling pathways.

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