Involvement of STAP-2 in Brk-mediated phosphorylation and activation of STAT5 in breast cancer cells
Involvement of STAP-2 in Brk-mediated phosphorylation and activation of STAT5 in breast cancer cells
复制标题
DOI：
10.1111/j.1349-7006.2010.01842.x
复制
发表时间：
2011-04-01
期刊：
影响因子：
5.7
通讯作者：
Matsuda, Tadashi
中科院分区：
文献类型：
--
作者：
Ikeda, Osamu;Mizushima, Akihiro;Matsuda, Tadashi
信号转导适配蛋白(STAP)-2是最近发现的一种包含Pleckstrin同源和Src同源2样结构域的适配蛋白，也是乳腺癌激酶（Brk）的底物。在之前的研究中，我们发现STAP-2上调brk介导的乳腺癌细胞中信号换能器和转录激活因子（STAT） 3的激活。在这里，我们研究了STAP-2在乳腺癌细胞中参与brk介导的STAT5激活。STAP-2异位表达诱导brk介导的STAT5转录活性。此外，在T47D乳腺癌细胞中，stap -2敲低诱导增殖明显减少，其强度与Brk-或stat5b敲低后相同。从机制上看，STAP-2的Pleckstrin同源结构域可能参与了Brk磷酸化激活STAT5的过程。综上所述，我们的研究结果为乳腺癌的新治疗策略的发展以及新的预后价值提供了见解。（癌症科学2011；102:756-761）
Signal-transducing adaptor protein (STAP)-2 is a recently identified adaptor protein that contains Pleckstrin homology and Src homology 2-like domains, and is also known to be a substrate of breast tumor kinase (Brk). In a previous study, we found that STAP-2 upregulated Brk-mediated activation of signal transducer and activator of transcription (STAT) 3 in breast cancer cells. Here, we examined the involvement of STAP-2 in Brk-mediated STAT5 activation in breast cancer cells. Ectopic expression of STAP-2 induced Brk-mediated transcriptional activity of STAT5. Furthermore, STAP-2-knockdown in T47D breast cancer cells induced a marked decrease in proliferation that was as strong as that after Brk- or STAT5b-knockdown. Regarding the mechanism, the Pleckstrin homology domain of STAP-2 is likely to participate in the process by which Brk phosphorylates and activates STAT5. Taken together, our findings provide insights toward the development of novel therapeutic strategies as well as novel prognostic values in breast carcinomas. (Cancer Sci 2011; 102: 756-761)