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

Kops, Geert J. P. L., Ruiter, Nancy D. de, De Vries-Smits, Alida M. M., Powell, David R., Bos, Johannes L., Burgering, Boudewijn M. Th.·1999·Nature
DOI 10.1038/19328
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Abstract

The phosphatidylinositol-3-OH-kinase (PI(3)K) effector protein kinase B regulates certain insulin-responsive genes, 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. Here we show that protein kinase B phosphorylates AFX, a human orthologue of daf-16, 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.

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Research works printed but not linked: 30

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Metadata

Authors
Kops, G. J. P. L., Ruiter, N. D. D., De Vries-Smits, A. M. M., Powell, D. R., Bos, J. L., & Burgering, B. M. T.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
1999-04
Volume
398
Issue
6728
Pages
630-634
ISSN
  • 0028-0836
  • 1476-4687
DOI
10.1038/19328
Cited by
882
References
0
Language
en
Licence
www.springer.com/tdm (tdm)

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