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Effect of multiple phosphorylation events on the transcription factors FKHR, FKHRL1 and AFX

Y L Woods1, G Rena

  • 1MRC Protein Phosphorylation Unit, School of Life Sciences, MSI/WTB Complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK.

Biochemical Society Transactions
|August 28, 2002
PubMed

Insights

The insulin signaling pathway, involving PI 3-kinase/PDK1/PKB, regulates cell survival. This pathway

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Metabolic Regulation

Background:

  • The phosphoinositide 3-kinase (PI 3-kinase)/3-phosphoinositide-dependent kinase-1 (PDK1)/protein kinase B (PKB) cascade is crucial for metabolic control and cell survival.
  • PKB mediates its effects through the phosphorylation of various downstream proteins.

Purpose of the Study:

  • To investigate the role of FKHR isoforms (FKHR, AFX, FKHRL1) as potential effectors in the PI 3-kinase/PDK1/PKB signaling pathway.
  • To understand how PKB influences the cellular localization and activity of FKHR isoforms.

Main Methods:

  • Cell-based assays to study protein phosphorylation.
  • Analysis of nuclear exclusion of transcription factors following pathway activation.

Main Results:

  • PKB phosphorylates FKHR isoforms (FKHR, AFX, FKHRL1) in cells.
  • Phosphorylation by PKB induces the nuclear exit of these FKHR isoforms.

Conclusions:

  • FKHR isoforms are likely critical downstream targets of the PI 3-kinase/PDK1/PKB pathway.
  • Regulation of FKHR isoform nuclear localization by PKB suggests a role in mediating the pathway's effects on gene expression and cellular processes.

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