Nature 1999,
PMID: 10217147
Kops, G J; de Ruiter, N D; De Vries-Smits, A M; Powell, D R; Bos, J L; Burgering, B M
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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Text Mining Data
Dashed line = No text mining data
Manually curated Databases
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IRef Hprd Interaction:
AKT1
—
FOXO4
(in vitro)
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IRef Hprd Interaction:
AKT1
—
FOXO4
(in vivo)
-
NCI Pathway Database Class I PI3K signaling events mediated by Akt:
FOXO1-3a-4/14-3-3 family complex (FOXO3_FOXO4_FOXO1-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB)
→
14-3-3 family (YWHAH/YWHAZ/YWHAQ/SFN/YWHAE/YWHAG/YWHAB)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database Class I PI3K signaling events mediated by Akt:
FOXO1-3a-4/14-3-3 family complex (FOXO3_FOXO4_FOXO1-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB)
→
FOXO1-3a-4-inactive (FOXO3/FOXO4/FOXO1)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database Class I PI3K signaling events mediated by Akt:
14-3-3 family (YWHAH/YWHAZ/YWHAQ/SFN/YWHAE/YWHAG/YWHAB)
→
FOXO1-3a-4-inactive (FOXO3/FOXO4/FOXO1)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction
In total, 56 gene pairs are associated to this article in curated databases