Related Experiment Video
Updated: Aug 24, 2026

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
FLT3 ligand regulates apoptosis through AKT-dependent inactivation of transcription factor FoxO3
Maria Jönsson1, Maria Engström, Jan-Ingvar Jönsson
1Division of Cell Biology, Department of Biomedicine and Surgery, Linköping University, Sweden.
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.
Related Concept Videos
PI3K/mTOR/AKT Signaling Pathway
The Intrinsic Apoptotic Pathway
The Extrinsic Apoptotic Pathway
TGF - β Signaling Pathway
Apoptosis
The JAK-STAT Signaling Pathway
