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Regulation of Akt/PKB activation by tyrosine phosphorylation

R Chen1, O Kim, J Yang

  • 1Department of Laboratory Medicine and Pathology and Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.

The Journal of Biological Chemistry
|July 11, 2001
PubMed

Insights

Growth factors activate Akt/PKB through phosphorylation. This study reveals tyrosine phosphorylation of Akt is crucial for its activation and biological functions, alongside Thr308 and Ser473 phosphorylation.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Akt/PKB activation by growth factors is critical for cellular processes.
  • Optimal Akt kinase activity depends on phosphorylation at Thr308 and Ser473.
  • The role of tyrosine phosphorylation in Akt activation is not fully understood.

Purpose of the Study:

  • To investigate the requirement of tyrosine phosphorylation for Akt activation.
  • To identify specific tyrosine residues involved in Akt activation.
  • To determine the functional significance of Akt tyrosine phosphorylation.

Main Methods:

  • Utilized epidermal growth factor (EGF) stimulation in various cell lines (COS1, PC3M, NIH3T3).
  • Employed PP2, a Src family tyrosine kinase inhibitor.
  • Generated and analyzed Akt tyrosine phosphorylation mutants (YF mutants).

Main Results:

  • EGF treatment induced Akt tyrosine phosphorylation, inhibited by PP2.
  • v-Src expression elevated Akt activity and tyrosine phosphorylation.
  • SYF cells lacking Src, Yes, and Fyn showed reduced Akt activity, restored by c-Src.
  • Mutating two specific tyrosine residues abolished growth factor-stimulated Akt activity and function.

Conclusions:

  • Tyrosine phosphorylation of Akt is essential for its activation by growth factors.
  • Specific tyrosine residues near the activation loop are critical for Akt kinase activity.
  • Akt tyrosine phosphorylation plays a vital role in mediating biological functions, including transcription factor activity and apoptosis regulation.

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