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Oligopeptide Competition Assay for Phosphorylation Site Determination
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Phosphorylation of Akt at the C-terminal tail triggers Akt activation

Pengda Liu1, Zhiwei Wang2, Wenyi Wei1

  • 1Department of Pathology; Beth Israel Deaconess Medical Center; Harvard Medical School; Boston, MA USA.

Cell Cycle (Georgetown, Tex.)
|June 17, 2014
PubMed

Insights

New research reveals that phosphorylation of Akt1 at S477 and T479 sites is crucial for its activation. These events, regulated by Cdk2/Cyclin A or mTORC2, offer novel insights into tumorigenesis.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Cancer Research

Background:

  • Aberrant activation of the protein kinase Akt is a key driver of tumorigenesis.
  • Akt activation is traditionally marked by phosphorylation at S477 and T308 by mTORC2 and PDK1.
  • Understanding novel activation mechanisms is critical for targeted cancer therapies.

Purpose of the Study:

  • To investigate the role of C-terminal phosphorylation (S477 and T479) in Akt1 activation.
  • To elucidate the regulatory mechanisms governing Akt1 S477/T479 phosphorylation.
  • To highlight the biological significance of these novel activation sites.

Main Methods:

  • Phosphorylation site analysis of Akt1.
  • Investigation of kinase involvement (Cdk2/Cyclin A, mTORC2).
  • Analysis of Akt1 activation under different cellular conditions.

Main Results:

  • Phosphorylation of Akt1 at S477 and T479 promotes its activation.
  • These phosphorylation events are regulated by Cdk2/Cyclin A during cell cycle progression.
  • mTORC2 also governs Akt1 pS477/pT479 under growth stimulation conditions.

Conclusions:

  • Akt1 activation is significantly influenced by C-terminal phosphorylation at S477/T479.
  • Distinct cellular contexts dictate the kinases responsible for these novel activation events.
  • These findings provide new perspectives on Akt signaling in cancer.
Keywords:
Cancer signalingCdk2/Cyclin AmTOR/Akt pathwaymTORC2phosphorylationprotein kinase

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