ABSTRACT
Stromal cell-derived factor-1 (SDF-1/CXCL12) enhances the survival of hematopoietic stem and progenitor cells in synergy with other cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), steel factor, and thrombopoietin (TPO), and both the PI3K/Akt and MAPK pathways have been linked to this survival. To further evaluate intracellular signaling involved in SDF-1/CXCL12 survival effects, we investigated modulation of downstream signaling molecules. The synergistic survival enhancement of SDF-1/CXCL12 plus other cytokines were directly linked to enhanced phosphorylation of p70/85S6K and cAMP responsive element binding protein (CREB), as well as enhanced induction of the Bcl-2 family member Mcl-1. Most prominently, c-Fos, a component of AP1 transcription factor, was synergistically induced by SDF-1/CXCL12 plus other cytokines. These results suggest that SDF-1/CXCL12 enhanced cell survival in synergy with other cytokines involves activation of CREB and induction of Mcl-1 and c-Fos.
