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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Analysis of synergism between stem cell factor and granulocyte-macrophage colony-stimulating factor on human megakaryoblastic cells: an increase in tyrosine phosphorylation of 145 kDa subunit of c-kit in two-factor combination.

In normal hematopoiesis, stem cell factor (SCF) stimulates survival, proliferation and differentiation of hematopoietic progenitors. Although SCF acts synergistically with a variety of cytokines, the mechanism of growth factor-cooperation remains to be determined. To analyze the synergism between SCF and granulocyte-macrophage colony- stimulating factor (GM-CSF), we established a new megakaryoblastic cell line, HML-2, by culture in the presence of both SCF and GM-CSF. While SCF alone or GM-CSF alone supported modest cell growth, SCF and GM-CSF together induced substantial growth of this cell line. SCF alone tyrosine- phosphorylated several bands including the 145 kDa subunit of c-kit. GM-CSF alone did not cause the tyrosine phosphorylation of the 145 kDa subunit, but markedly up-regulated the expression of the 145 kDa subunit of c-kit. The combination of SCF and GM-CSF resulted in a synergistic increase in tyrosine phosphorylation of the 145 kDa subunit of c-kit. Several proliferation inhibitors which removed the two-factor interaction on the growth of the HML-2 cells down-regulated the 145 kDa subunit of c-kit. Thus, a synergistic increase in tyrosine phosphorylation of the 145 kDa subunit of c-kit may be one possible mechanism underlying the cooperation of SCF and GM-CSF on the HML-2 cell growth.[1]

References

  1. Analysis of synergism between stem cell factor and granulocyte-macrophage colony-stimulating factor on human megakaryoblastic cells: an increase in tyrosine phosphorylation of 145 kDa subunit of c-kit in two-factor combination. Kamijo, T., Koike, K., Takeuchi, K., Higuchi, T., Sawai, N., Kikuchi, T., Tsumura, H., Akiyama, H., Koike, T., Ishii, E., Komiyama, A. Leuk. Res. (1997) [Pubmed]
 
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