The BCR-ABL tyrosine kinase inhibits apoptosis by activating a Ras-dependent signaling pathway.
The BCR-ABL tyrosine kinase inhibits apoptosis by activating a Ras-dependent signaling pathway.
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发表时间：
1996-12
期刊：
影响因子：
8
通讯作者：
D. Cortez;G. Stoica;Pierce Jh;A. Pendergast
中科院分区：
文献类型：
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作者：
D. Cortez;G. Stoica;Pierce Jh;A. Pendergast
BCR-ABL是一种失调的酪氨酸激酶，在费城染色体（Ph 1）阳性的人类白血病中表达。当在造血细胞中表达时，BCR-ABL引起细胞因子非依赖性增殖，诱导致瘤性生长，并防止细胞因子剥夺或DNA损伤引起的细胞凋亡。BCR-ABL在细胞中传递信号的一种机制是通过激活小鸟嘌呤核苷酸结合蛋白Ras。BCR-ABL转化细胞具有组成性高水平的活性GTP结合Ras。在这里，我们使用32 D细胞，诱导表达显性负Ras蛋白，以确定在BCR-ABL转化细胞的Ras需求。显性负性Ras抑制BCR-ABL介导的Ras活化，并通过凋亡机制诱导细胞死亡。因此，BCR-ABL通过激活Ras依赖性信号通路抑制细胞凋亡。
BCR-ABL is a deregulated tyrosine kinase that is expressed in Philadelphia chromosome (Ph1) positive human leukemias. When expressed in hematopoietic cells, BCR-ABL causes cytokine independent proliferation, induces tumorigenic growth and prevents apoptosis in response to cytokine deprivation or DNA damage. One mechanism by which BCR-ABL signals in cells is by activating the small guanine nucleotide binding protein Ras. BCR-ABL-transformed cells have constitutively high levels of active, GTP-bound Ras. Here we use 32D cells that inducibly express a dominant negative Ras protein to define the Ras requirements in BCR-ABL-transformed cells. Dominant negative Ras inhibits BCR-ABL-mediated Ras activation, and induces cell death by an apoptotic mechanism. Therefore, BCR-ABL inhibits apoptosis through activation of a Ras-dependent signaling pathway.