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FLT3 ligand regulates apoptosis through AKT-dependent inactivation of transcription factor Fox03

Jonsson, M; Kraft, Maria LU and Jönsson, Jan-Ingvar LU (2004) In Biochemical and Biophysical Research Communications 318(4). p.899-903
Abstract
Proliferation, differentiation, and survival of hematopoietic cells are regulated by cytokines, acting through specific receptors. FLT3 ligand (FL) is one of the most important cytokines for regulation of the hematopoietic system, and its receptor FLT3 is expressed on both stem cells and progenitors. Regulation of Forkhead transcription factors has been described as an important mechanism to control apoptosis and cell cycle progression in hematopoietic progenitors. Here we report that FL induces AKT/PKB activation, which in turn phosphorylates and thereby inactivates the Forkhead protein FoxO3 in the progenitor cell line FDC-P1 stably expressing murine FLT3 receptor. Phosphorylation of AKT and FoxO3 was blocked by the PI-3 kinase inhibitor... (More)
Proliferation, differentiation, and survival of hematopoietic cells are regulated by cytokines, acting through specific receptors. FLT3 ligand (FL) is one of the most important cytokines for regulation of the hematopoietic system, and its receptor FLT3 is expressed on both stem cells and progenitors. Regulation of Forkhead transcription factors has been described as an important mechanism to control apoptosis and cell cycle progression in hematopoietic progenitors. Here we report that FL induces AKT/PKB activation, which in turn phosphorylates and thereby inactivates the Forkhead protein FoxO3 in the progenitor cell line FDC-P1 stably expressing murine FLT3 receptor. Phosphorylation of AKT and FoxO3 was blocked by the PI-3 kinase inhibitor LY294002 but not by the MAP kinase inhibitor PD98059. Expression of a mutated FoxO3, in which all three inhibitory phosphorylation sites were mutated to alanine, led to rapid increase of apoptotic cells in the presence of FL. These results suggest that FL-induced regulation of apoptosis is executed by FoxO3. (C) 2004 Elsevier Inc. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
survival, signaling, FLT3, hematopoiesis, cytokines, AKT, forkhead
in
Biochemical and Biophysical Research Communications
volume
318
issue
4
pages
899 - 903
publisher
Elsevier
external identifiers
  • wos:000221776400015
  • pmid:15147956
  • scopus:2442563747
ISSN
1090-2104
DOI
10.1016/j.bbrc.2004.04.110
language
English
LU publication?
yes
id
4fe140c5-7ee2-421b-b7ad-8f5f68492c3b (old id 276792)
date added to LUP
2007-10-23 17:48:03
date last changed
2017-01-08 04:55:42
@article{4fe140c5-7ee2-421b-b7ad-8f5f68492c3b,
  abstract     = {Proliferation, differentiation, and survival of hematopoietic cells are regulated by cytokines, acting through specific receptors. FLT3 ligand (FL) is one of the most important cytokines for regulation of the hematopoietic system, and its receptor FLT3 is expressed on both stem cells and progenitors. Regulation of Forkhead transcription factors has been described as an important mechanism to control apoptosis and cell cycle progression in hematopoietic progenitors. Here we report that FL induces AKT/PKB activation, which in turn phosphorylates and thereby inactivates the Forkhead protein FoxO3 in the progenitor cell line FDC-P1 stably expressing murine FLT3 receptor. Phosphorylation of AKT and FoxO3 was blocked by the PI-3 kinase inhibitor LY294002 but not by the MAP kinase inhibitor PD98059. Expression of a mutated FoxO3, in which all three inhibitory phosphorylation sites were mutated to alanine, led to rapid increase of apoptotic cells in the presence of FL. These results suggest that FL-induced regulation of apoptosis is executed by FoxO3. (C) 2004 Elsevier Inc. All rights reserved.},
  author       = {Jonsson, M and Kraft, Maria and Jönsson, Jan-Ingvar},
  issn         = {1090-2104},
  keyword      = {survival,signaling,FLT3,hematopoiesis,cytokines,AKT,forkhead},
  language     = {eng},
  number       = {4},
  pages        = {899--903},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {FLT3 ligand regulates apoptosis through AKT-dependent inactivation of transcription factor Fox03},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2004.04.110},
  volume       = {318},
  year         = {2004},
}