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Direct control of the Forkhead transcription factor AFX by protein kinase B

Author

Listed:
  • Geert J. P. L. Kops

    (Laboratory for Physiological Chemistry and Centre for Biomedical Genetics, University of Utrecht)

  • Nancy D. de Ruiter

    (Laboratory for Physiological Chemistry and Centre for Biomedical Genetics, University of Utrecht)

  • Alida M. M. De Vries-Smits

    (Laboratory for Physiological Chemistry and Centre for Biomedical Genetics, University of Utrecht)

  • David R. Powell

    (Baylor College of Medicine)

  • Johannes L. Bos

    (Laboratory for Physiological Chemistry and Centre for Biomedical Genetics, University of Utrecht)

  • Boudewijn M. Th. Burgering

    (Laboratory for Physiological Chemistry and Centre for Biomedical Genetics, University of Utrecht)

Abstract

The phosphatidylinositol-3-OH-kinase (PI(3)K) effector protein kinase B (refs 1, 2) regulates certain insulin-responsive genes3,4, but the transcription factors regulated by protein kinase B have yet to be identified. Genetic analysis in Caenorhabditis elegans has shown that the Forkhead transcription factor daf -16 is regulated by a pathway consisting of insulin-receptor-like daf- 2 and PI(3)K-like age -1 (5–8). Here we show that protein kinase B phosphorylates AFX, a human orthologue of daf -16 (refs 5, 6, 9), both in vitro and in vivo. Inhibition of endogenous PI(3)K and protein kinase B activity prevents protein kinase B-dependent phosphorylation of AFX and reveals residual protein kinase B-independent phosphorylation that requires Ras signalling towards the Ral GTPase. In addition, phosphorylation of AFX by protein kinase B inhibits its transcriptional activity. Together, these results delineate a pathway for PI(3)K-dependent signalling to the nucleus.

Suggested Citation

  • Geert J. P. L. Kops & Nancy D. de Ruiter & Alida M. M. De Vries-Smits & David R. Powell & Johannes L. Bos & Boudewijn M. Th. Burgering, 1999. "Direct control of the Forkhead transcription factor AFX by protein kinase B," Nature, Nature, vol. 398(6728), pages 630-634, April.
    • Handle: RePEc:nat:nature:v:398:y:1999:i:6728:d:10.1038_19328
    DOI: 10.1038/19328
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