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Published on: December 21, 2011

Molecular pathways leading to oxidative stress-induced phosphorylation of Akt

Michelle M Lahair1, Christopher J Howe, Oswaldo Rodriguez-Mora

  • 1Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27834, USA.

Antioxidants & Redox Signaling
|September 22, 2006
PubMed

Insights

Oxidative stress activates distinct pathways for Akt phosphorylation. Hydrogen peroxide triggers Akt phosphorylation at T308 via CaM-Ks, independent of PI3K. Akt phosphorylation at S473 requires CaM-K, PI3K, and Src activity.

Area of Science:

  • Cellular signaling
  • Oxidative stress response
  • Protein phosphorylation

Background:

  • Oxidative stress activates intracellular signaling pathways.
  • Previous work showed CaM-K inhibitor KN-93 blocked hydrogen peroxide-induced Akt phosphorylation at T308.
  • Akt (Protein Kinase B) is a key regulator of cellular processes.

Purpose of the Study:

  • To elucidate the specific signaling pathways involved in hydrogen peroxide-induced Akt phosphorylation at T308 and S473.
  • To determine the roles of PI3K, CaM-K, and Src kinases in these phosphorylation events.

Main Methods:

  • Utilized Jurkat T lymphocytes treated with hydrogen peroxide.
  • Investigated the effects of inhibitors LY294002 (PI3K inhibitor) and KN-93 (CaM-K inhibitor).
  • Assessed the role of p56(Lck) (a Src kinase) in Akt phosphorylation.

Main Results:

  • Hydrogen peroxide-induced Akt phosphorylation at T308 was PI3K-independent but CaM-K dependent.
  • Hydrogen peroxide-induced Akt phosphorylation at S473 was dependent on both PI3K and CaM-K.
  • p56(Lck) played a significant role in S473 phosphorylation but a minimal role in T308 phosphorylation.

Conclusions:

  • Two distinct pathways are activated by hydrogen peroxide in Jurkat T lymphocytes, converging on Akt phosphorylation.
  • One pathway phosphorylates Akt T308 via CaM-Ks, independent of PI3K and Src kinases.
  • A second pathway phosphorylates Akt S473, requiring CaM-K, PI3K, and Src kinase activity.

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