Thirty-eight-negative kinase 1 (TNK1) facilitates TNFα-induced apoptosis by blocking NF-κB activation
Thirty-eight-negative kinase 1 (TNK1) facilitates TNFα-induced apoptosis by blocking NF-κB activation
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DOI：
10.1038/sj.onc.1210476
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发表时间：
2007-10-01
期刊：
影响因子：
8
通讯作者：
Seufferlein, T.
中科院分区：
文献类型：
--
作者：
Azoitei, N.;Brey, A.;Seufferlein, T.
38-Negative Kinase 1(TNK1)是非受体酪氨酸激酶ACK家族的成员，最初是从CD34+/Lin-/CD38-造血干/祖细胞中克隆的。TNK1诱导的信号通路在很大程度上是未知的。在这里，我们报告了TNK1的表达和随后的激活通过选择性地抑制肿瘤坏死因子α诱导的核因子-kappa B(NF-kappa B)的激活而使肿瘤坏死因子a(TNFα)诱导的细胞凋亡。TNK1对核因子-kappaB的DNA结合或核因子-kappa B复合体的组成没有影响，但该激酶显著阻止了TNFa诱导的核因子-kappaB反式激活。因此，TNK1作为一种新的分子开关，可以决定TNFa信号的性质，从而决定细胞死亡。
Thirty-eight-negative kinase 1 (TNK1) is a member of the ACK-family of nonreceptor tyrosine kinases and was originally cloned from CD34+/Lin-/CD38-hematopoietic stem/progenitor cells. The signaling pathways induced by TNK1 are largely unknown. Here, we report that expression and consequent activation of TNK1 enables tumor necrosis factor a (TNF alpha)-induced apoptosis by selectively inhibiting TNF alpha-induced activation of nuclear factor-kappa B (NF-kappa B). TNK1 has no effect on NF-kappa B DNA binding or the composition of the NF-kappa B complex; however, the kinase markedly prevents TNFa-induced NF-kappa B transactivation. TNK1 therefore acts as a novel molecular switch that can determine the properties of TNFa signaling and therefore cell death.