Regulation of Bcl-2 expression by oncogenic Ras protein in hematopoietic cells.
Regulation of Bcl-2 expression by oncogenic Ras protein in hematopoietic cells.
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发表时间：
1995-06
期刊：
影响因子：
8
通讯作者：
T. Kinoshita;Takashi Yokota;Ken-ichi Arai;Atsushi Miyajima
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作者：
T. Kinoshita;Takashi Yokota;Ken-ichi Arai;Atsushi Miyajima
白细胞介素3（IL-3）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）可诱导造血细胞DNA合成，抑制造血细胞凋亡。IL-3/GM-CSF通过共同受体亚基的不同结构域激活多个信号级联发挥多效性功能。正如我们以前报道的，Ras信号通路在抑制IL-3依赖性造血细胞的凋亡而不是刺激DNA合成中起着关键作用。为了阐明Ras诱导细胞存活的分子基础，我们研究了Ras激活对Bcl-2及其相关分子表达的影响。通过使用可诱导的致癌Ras激活Ras通路导致bcl-2和bcl-xL的快速上调，并且表达水平几乎等同于在生长细胞中观察到的表达水平。另一方面，bax的表达，拮抗bcl-2同源物，不受致癌Ras或IL-3剥夺。因此，Ras途径调节Bcl-2及其相关存活蛋白的表达，这似乎是IL-3/GM-CSF通过激活Ras途径抑制细胞凋亡的机制的基础。
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.