Enhancement of cell survival by stromal cell-derived factor-1/CXCL12 involves activation of CREB and induction of Mcl-1 and c-Fos in factor-dependent human cell line MO7e

Eun Kyoung Joo, Hal E. Broxmeyer, Hyung Joo Kwon, Bum Kang Ho, Sook Kim Jin, Seok Lim Jong, Yong Kyoung Choe, Seong Choe In, Keun Myung Pyung, Younghee Lee

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)563-570
Number of pages8
JournalStem Cells and Development
Volume13
Issue number5
DOIs
StatePublished - Oct 1 2004

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

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