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FLT3 ligand regulat...
FLT3 ligand regulates apoptosis through AKT-dependent inactivation of transcription factor Fox03
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- Jönsson, Maria, 1977- (author)
- Linköpings universitet,Hälsouniversitetet,Avdelningen för medicinsk cellbiologi
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- Kraft, Maria (author)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine
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- Jönsson, Jan-Ingvar (author)
- Linköpings universitet,Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine,Hälsouniversitetet,Avdelningen för medicinsk cellbiologi
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- Engström, Maria, 1973- (author)
- Linköpings universitet,Hälsouniversitetet,Avdelningen för medicinsk cellbiologi
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(creator_code:org_t)
- Elsevier BV, 2004
- 2004
- English.
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In: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 318:4, s. 899-903
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Abstract
Subject headings
Close
- 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.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Keyword
- survival
- signaling
- FLT3
- hematopoiesis
- cytokines
- AKT
- forkhead
- MEDICINE
Publication and Content Type
- art (subject category)
- ref (subject category)
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