ZIP kinase, a novel serine/threonine kinase which mediates apoptosis
ZIP kinase, a novel serine/threonine kinase which mediates apoptosis
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DOI：
10.1128/mcb.18.3.1642
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发表时间：
1998-03-01
影响因子：
5.3
通讯作者：
Akira, S
中科院分区：
文献类型：
--
作者：
Kawai, T;Matsumoto, M;Akira, S
我们发现了一种新型的丝/苏激酶，命名为ZIP激酶，它介导细胞凋亡，除了N末端的激酶结构域外，ZIP激酶在其C末端含有亮氨酸拉链结构，ZIP激酶物理结合ATF 4，ATF 4是转录激活因子/环AMP响应元件结合蛋白的成员（ATF/CREB）家族，通过其亮氨酸拉链之间的相互作用，亮氨酸拉链结构域对于ZIP激酶的同源二聚化以及激酶的激活是必需的，免疫染色研究表明ZIP激酶定位于细胞核，过表达完整的ZIP激酶而不是无催化活性的激酶突变体导致NIH 3 T3细胞凋亡的形态学变化，表明ZIP激酶的细胞死亡诱导活性依赖于其内在的激酶活性。有趣的是，ZIP激酶的催化结构域与死亡相关蛋白激酶（DAP激酶）的催化结构域密切相关，死亡相关蛋白激酶（DAP激酶）是γ干扰素诱导的细胞凋亡的介导剂，因此，ZIP和DAP激酶都代表了一个新的激酶家族，其通过其催化活性介导细胞凋亡。
We have identified a novel serine/threonine kinase, designated ZIP kinase, which mediates apoptosis, ZIP kinase contains a leucine zipper structure at its C terminus, in addition to a kinase domain at its N terminus, ZIP kinase physically binds to ATF4, a member of the activating transcription factor/cyclic AMP-responsive element-binding protein (ATF/CREB) family, through interaction between their leucine zippers, The leucine zipper domain is necessary for the homodimerization of ZIP kinase as well as for the activation of kinase, Immunostaining study showed that ZIP kinase localizes in the nuclei, Overexpression of intact ZIP kinase but not catalytically inactive kinase mutants led to the morphological changes of apoptosis in NIH 3T3 cells, suggesting that the cell death-inducing activity of ZIP kinase depends on its intrinsic kinase activity. Interestingly, the catalytic domain of ZIP kinase is closely related to that of death-associated protein kinase (DAP kinase), which is a mediator of apoptosis induced by gamma interferon, Therefore, both ZIP and DAP kinases represent a novel kinase family, which mediates apoptosis through their catalytic activities.