Direct control of the forkhead transcription faotor AFX by protein kinase B

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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

895 Citations (Scopus)


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 (refs 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 vive. 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 Ra1 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.

Original languageEnglish
Pages (from-to)630-634
Number of pages5
Issue number6728
Publication statusPublished - 15 Apr 1999


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