Regulation of Bcl-2 expression by oncogenic Ras protein in hematopoietic cells.
Interleukin 3 (IL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF) induce DNA synthesis and suppress apoptosis of hematopoietic cells. IL-3/GM-CSF exert pleiotropic functions by activating multiple signaling cascades through distinct domains of the common receptor subunit. As we previously reported, the Ras signaling pathway plays a pivotal role in suppressing apoptotic death rather than stimulating DNA synthesis in IL-3 dependent hematopoietic cells. In order to clarify the molecular basis of Ras-induced cell survival, we investigated the effect of Ras activation on the expression of Bcl-2 and its related molecules. Activation of the Ras pathway by using an inducible oncogenic Ras resulted in the rapid up-regulation of bcl-2 and bcl-xL, and the level of expression was nearly equivalent to that observed in growing cells. On the other hand, expression of bax, an antagonistic bcl-2 homologue, was not affected by oncogenic Ras or IL-3-deprivation. Thus, the Ras pathway regulates the expression of Bcl-2 and its related survival protein, and this appears to underlie the mechanism by which IL-3/GM-CSF inhibit apoptosis through activation of the Ras pathway.
Kinoshita
T
T
Department of Cell Biology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304, USA.
Yokota
T
T
Arai
K
K
Miyajima
A
A
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D018076:DNA, Complementary; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D014162:Transfection; D018631:ras Proteins / Q000235:genetics / Q000502:physiology*
D018076:DNA, Complementary; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018631:ras Proteins