Expression and oncogenic role of Brk (PTK6/Sik) protein tyrosine kinase in lymphocytes
Expression and oncogenic role of Brk (PTK6/Sik) protein tyrosine kinase in lymphocytes
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DOI：
10.2353/ajpath.2006.050521
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发表时间：
2006-05-01
影响因子：
6
通讯作者：
Wasik, MA
中科院分区：
文献类型：
--
作者：
Kasprzycka, M;Majewski, M;Wasik, MA
酪氨酸激酶在细胞的增殖、存活、黏附和运动中起着重要的作用，也被证明可以介导恶性细胞的转化。在这里，我们描述了蛋白酪氨酸激酶BRK在很大比例的皮肤T细胞淋巴瘤和其他转化的T和B细胞群体中的结构性表达。该激酶在核定位和激活状态下表达。在正常T细胞被激活时，BRK也被诱导表达。BRK基因的导入表达显著降低了BaF3淋巴细胞在体外增殖和存活方面对细胞因子和生长因子的依赖。BRK还赋予BaF3细胞体内致瘤性。SiRNA介导的对恶性T细胞内源性BRK的抑制降低了其生长和存活能力。这些发现证明了BRK在正常T淋巴细胞中的诱导表达，以及在恶性T和B细胞中的持续表达。此外，我们的结果表明，BRK可能在淋巴肿瘤的发生中发挥关键作用，从而将该激酶确定为淋巴瘤的潜在治疗靶点。
Tyrosine kinases play a fundamental role in cell proliferation, survival, adhesion, and motility and have also been shown to mediate malignant cell transformation. Here we describe constitutive expression of the protein tyrosine kinase Brk in a large proportion of cutaneous T-cell lymphomas and other transformed T- and B-cell populations. The kinase is expressed in the nuclear localization and activated state. Brk expression was also induced in normal T cells on their activation. Introduced expression of the Brk gene resulted in markedly diminished cytokine and growth factor dependence of transfected BaF3 lymphocytes in regard to their in vitro proliferation and survival. Brk also conferred in vivo oncogenicity on the BaF3 cells. siRNA-mediated inhibition of the endogenous Brk in malignant T cells diminished their growth and survival capacity. These findings document inducible expression of Brk in normal T lymphocytes and persistent expression of the activated kinase in malignant T and B cells. Furthermore, our results indicate that Brk may play a key role in lymphomagenesis, hence identifying the kinase as a potential therapeutic target in lymphomas.