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.
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.
Joo
Eun-Kyoung
EK
Department of Biochemistry, Biotechnology Research Institute, Chungbuk National University, Cheongju, Chungbuk, 361-763, Korea.
Broxmeyer
Hal E
HE
Kwon
Hyung-Joo
HJ
Kang
Ho Bum
HB
Kim
Jin Sook
JS
Lim
Jong Seok
JS
Choe
Yong-Kyoung
YK
Choe
In Seong
IS
Myung
Pyung Keun
PK
Lee
Younghee
Y
D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D017362:Cyclic AMP Response Element-Binding Protein; D016207:Cytokines; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000242:Cyclic AMP; D038762:Ribosomal Protein S6 Kinases, 70-kDa