Targeting of the c-Ab1 tyrosine kinase to mitochondria in the necrotic cell death response to oxidative stress
Targeting of the c-Ab1 tyrosine kinase to mitochondria in the necrotic cell death response to oxidative stress
复制标题
DOI：
10.1074/jbc.m101414200
复制
发表时间：
2001-05-18
影响因子：
4.8
通讯作者：
Kufe, D
中科院分区：
文献类型：
--
作者：
Kumar, S;Bharti, A;Kufe, D
普遍表达的c-Abl酪氨酸激酶在细胞对基因毒性和氧化应激的反应中被激活。本研究表明活性氧（ROS）诱导c-Abl靶向线粒体。我们发现ros诱导的C - abl定位于线粒体依赖于蛋白激酶C (PKC)S的激活和C - abl激酶功能。c-Abl靶向线粒体与ros诱导的线粒体跨膜电位丧失有关。结果还表明，c-Abl对于ros诱导的ATP耗竭和坏死样细胞死亡的激活是必需的。这些发现表明，c-Abl激酶在氧化应激反应中靶向线粒体，从而介导线粒体功能障碍和细胞死亡。
The ubiquitously expressed c-Abl tyrosine kinase is activated in the response of cells to genotoxic and oxidative stress. The present study demonstrates that reactive oxygen species (ROS) induce targeting of c-Abl to mitochondria. We show that ROS-induced localization of c-Abl to mitochondria is dependent on activation of protein kinase C (PKC)S and the c-Abl kinase function. Targeting of c-Abl to mitochondria is associated with ROS-induced loss of mitochondrial transmembrane potential. The results also demonstrate that c-Abl is necessary for ROS-induced depletion of ATP and the activation of a necrosis-like cell death. These findings indicate that the c-Abl kinase targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death.