Binding of Ku and c-Abl at the kinase homology region of DNA-dependent protein kinase catalytic subunit
Binding of Ku and c-Abl at the kinase homology region of DNA-dependent protein kinase catalytic subunit
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DOI：
10.1074/jbc.272.40.24763
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发表时间：
1997-10-03
影响因子：
4.8
通讯作者：
Weaver, DT
中科院分区：
文献类型：
--
作者：
Jin, SF;Kharbanda, S;Weaver, DT
DNA依赖蛋白激酶(DNA-PK)控制着哺乳动物细胞双链DNA断裂的修复。DNA-PK的蛋白激酶亚基(DNA-PKcs)通过与Hu DNA结合的异源二聚体作用于DNA断裂。在这里，我们发现在DNA-PKcs(氨基酸3002-3850)的羧基末端存在一个Ku结合位点，靠近蛋白激酶结构域。相应地，与DNA-PK结合的核c-Abl酪氨酸激酶也与该蛋白的同源结构域结合。C-Abl SH3结构域与DNA-PKcs的3414-3850位氨基酸结合。C-Abl可磷酸化DNA-PKcs的C-末端片段，特别是3414-3850个氨基酸。DNA-PKcs的c-Abl磷酸化解离DNA-PKcs.Ku复合体。因此，Ku和c-Abl在DNA-PK活性方面提供了相反的功能。
The DNA-dependent protein kinase (DNA-PK) con trols the repair of double-stranded DNA breaks in mammalian cells. The protein kinase subunit of DNA-PK (DNA-PKcs) is targeted to DNA breaks by association with the Hu DNA-binding heterodimer. Here we show that a Ku association site is present at the carboxyl terminus of DNA-PKcs (amino acids 3002-3850) near the protein kinase domain. Correspondingly, the nuclear c-Abl tyrosine kinase that associates with DNA-PK also binds to the kinase homology domain. The c-Abl SH3 domain binds to amino acids 3414-3850 of DNA-PKcs. c-Abl phosphorylates C-terminal fragments of DNA-PKcs, particularly amino acids 3414-3850. c-Abl phosphorylation of DNA-PKcs disassociates the DNA-PKcs.Ku complex. Thus, Ku and c-Abl provide opposing functions with regard to DNA-PK activity.