PMID- 10377430
OWN - NLM
STAT- MEDLINE
DCOM- 19990719
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 13
DP  - 1999 Jun 22
TI  - Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the
      winged helix transcription factor FKHR1.
PG  - 7421-6
AB  - Although genetic analysis has demonstrated that members of the winged helix, or
      forkhead, family of transcription factors play pivotal roles in the regulation of
      cellular differentiation and proliferation, both during development and in the
      adult, little is known of the mechanisms underlying their regulation. Here we
      show that the activation of phosphatidylinositol 3 (PI3) kinase by extracellular 
      growth factors induces phosphorylation, nuclear export, and transcriptional
      inactivation of FKHR1, a member of the FKHR subclass of the forkhead family of
      transcription factors. Protein kinase B (PKB)/Akt, a key mediator of PI3 kinase
      signal transduction, phosphorylated recombinant FKHR1 in vitro at threonine-24
      and serine-253. Mutants FKHR1(T24A), FKHR1(S253A), and FKHR1(T24A/S253A) were
      resistant to both PKB/Akt-mediated phosphorylation and PI3 kinase-stimulated
      nuclear export. These results indicate that phosphorylation by PKB/Akt negatively
      regulates FKHR1 by promoting export from the nucleus.
FAU - Biggs, W H 3rd
AU  - Biggs WH 3rd
AD  - The Ludwig Institute for Cancer Research, University of California, San Diego, La
      Jolla, CA 92093-0660, USA. wbiggs@ucsd.edu
FAU - Meisenhelder, J
AU  - Meisenhelder J
FAU - Hunter, T
AU  - Hunter T
FAU - Cavenee, W K
AU  - Cavenee WK
FAU - Arden, K C
AU  - Arden KC
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Biological Transport/genetics
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Gene Expression Regulation
MH  - Mutation
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - *Protein-Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Recombinant Proteins/genetics/metabolism
MH  - Transcription Factors/genetics/*metabolism
PMC - PMC22101
EDAT- 1999/06/23 10:00
MHDA- 2001/03/28 10:01
CRDT- 1999/06/23 10:00
PHST- 1999/06/23 10:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/06/23 10:00 [entrez]
AID - 10.1073/pnas.96.13.7421 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7421-6. doi:
      10.1073/pnas.96.13.7421.