PMID- 10217147
OWN - NLM
STAT- MEDLINE
DCOM- 19990610
LR  - 20111117
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 398
IP  - 6728
DP  - 1999 Apr 15
TI  - Direct control of the Forkhead transcription factor AFX by protein kinase B.
PG  - 630-4
AB  - 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.
FAU - Kops, G J
AU  - Kops GJ
AD  - Laboratory for Physiological Chemistry and Centre for Biomedical Genetics,
      University of Utrecht, The Netherlands.
FAU - de Ruiter, N D
AU  - de Ruiter ND
FAU - De Vries-Smits, A M
AU  - De Vries-Smits AM
FAU - Powell, D R
AU  - Powell DR
FAU - Bos, J L
AU  - Bos JL
FAU - Burgering, B M
AU  - Burgering BM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Blood Proteins)
RN  - 0 (FOXO4 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Blood Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - Cloning, Molecular
MH  - Humans
MH  - Insulin/metabolism
MH  - Mice
MH  - Phosphorylation
MH  - *Protein-Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Transcription Factors/antagonists & inhibitors/genetics/*metabolism
MH  - Tumor Cells, Cultured
MH  - ras Proteins/metabolism
EDAT- 1999/04/27 02:02
MHDA- 2001/03/23 10:01
CRDT- 1999/04/27 02:02
PHST- 1999/04/27 02:02 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/04/27 02:02 [entrez]
AID - 10.1038/19328 [doi]
PST - ppublish
SO  - Nature. 1999 Apr 15;398(6728):630-4. doi: 10.1038/19328.