Consequences of Shb and c-Abl interactions for cell death in response to various stress stimuli
Consequences of Shb and c-Abl interactions for cell death in response to various stress stimuli
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DOI：
10.1016/j.yexcr.2006.10.011
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发表时间：
2007-01-15
影响因子：
3.7
通讯作者：
Welsh, Michael
中科院分区：
文献类型：
--
作者：
Hagerkvist, Robert;Mokhtari, Dariush;Welsh, Michael
衔接蛋白Shb先前已被证明可以调节细胞凋亡，以响应细胞因子和血管生成抑制剂，尽管这些作用的机制仍然不清楚。我们目前证明了Shb和c-AbI之间的相互作用，Shb调节c-AbI激酶活性。这些数据表明，c-Abl结合酪氨酸磷酸化的Shb通过一个共同的努力，涉及c-Abl SH 3和SH 2结构域。Shb/c-Abl相互作用的生物学意义目前在过表达实验中进行了测试，发现其促进过氧化氢诱导的细胞死亡。我们还表明，Shb基因敲低实验，Shb调节c-AbI活性和调节细胞死亡的遗传毒性剂顺铂和内质网应激诱导剂衣霉素。这些发现与Shb在调节c-Abl促凋亡信号转导中响应于各种应激刺激起关键作用的概念一致。(c)2006年爱思唯尔公司All rights reserved.
The adaptor protein Shb has previously been shown to regulate apoptosis in response to cytokines and inhibitors of angiogenesis although the mechanisms governing these effects have remained obscure. We currently demonstrate interactions between Shb and c-AbI and that Shb regulates c-AbI kinase activity. The data suggest that c-Abl binds to tyrosine phosphorylated Shb via a concerted effort involving both the c-AbI SH3 and SH2 domains. The biological significance of the Shb/c-Abl interaction was presently tested in overexpression experiments and was found to promote hydrogen peroxide-induced cell death. We also show by Shb knockdown experiments that Shb regulates c-AbI activity and modulates cell death in response to the genotoxic agent cisplatin and the endoplasmic reticulum stress-inducer tunicamycin. The findings are in agreement with the notion of Shb playing a pivotal role in modulating c-Abl pro-apoptotic signaling in response to various stress stimuli. (c) 2006 Elsevier Inc. All rights reserved.