期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 278, 期 15, 页码 12961-12967出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M300058200
关键词
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The AbI family of mammalian nonreceptor tyrosine kinases consists of c-Abl and Arg. Recent work has shown that c-Abl and Arg are activated in the cellular response to oxidative stress. The present studies demonstrate that reactive oxygen species (ROS) induce the formation of c-Abl and Arg heterodimers. The results show that the c-Abl SH3 domain binds directly to a proline-rich site (amino acids 567-576) in the Arg C-terminal region. Formation of c-Abl(.)Arg heterodimers also involves direct binding of the Arg Src homology 3 domain to the C-terminal region of c-Abl. The results further demonstrate that the interaction between c-Abl and Arg involves c-Abl-mediated phosphorylation of Arg. The functional significance of the c-Abl-Arg interaction is supported by the demonstration that both c-Abl and Arg are required for ROS-induced apoptosis. These findings indicate that ROS induce c-Abl(.)Arg heterodinters and that both c-Abl and Arg are necessary as effectors in the apoptotic response to oxidative stress.
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