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Lyn酪氨酸激酶对DNA依赖性蛋白激酶的调控。

Regulation of DNA-dependent protein kinase by the Lyn tyrosine kinase.

作者信息

Kumar S, Pandey P, Bharti A, Jin S, Weichselbaum R, Weaver D, Kufe D, Kharbanda S

机构信息

Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

出版信息

J Biol Chem. 1998 Oct 2;273(40):25654-8. doi: 10.1074/jbc.273.40.25654.

DOI:10.1074/jbc.273.40.25654
PMID:9748231
Abstract

The Src-like protein-tyrosine kinase Lyn is activated by ionizing radiation and certain other DNA-damaging agents, whereas the DNA-dependent protein kinase (DNA-PK), consisting of the catalytic subunits (DNA-PKcs) and Ku DNA-binding components, requires DNA double-stranded breaks for activation. Here we demonstrate that Lyn associates constitutively with DNA-PKcs. The SH3 domain of Lyn interacts directly with DNA-PKcs near a leucine zipper homology domain. We also show that Lyn phosphorylates DNA-PKcs but not Ku in vitro. The interaction between Lyn and DNA-PKcs inhibits DNA-PKcs activity and the ability of DNA-PKcs to form a complex with Ku/DNA. These results support the hypothesis that there are functional interactions between Lyn and DNA-PKcs in the response to DNA damage.

摘要

Src 样蛋白酪氨酸激酶 Lyn 可被电离辐射及某些其他 DNA 损伤剂激活，而由催化亚基（DNA-PKcs）和 Ku DNA 结合成分组成的 DNA 依赖性蛋白激酶（DNA-PK），其激活需要 DNA 双链断裂。在此，我们证明 Lyn 与 DNA-PKcs 组成性结合。Lyn 的 SH3 结构域在亮氨酸拉链同源结构域附近直接与 DNA-PKcs 相互作用。我们还表明，Lyn 在体外可使 DNA-PKcs 磷酸化，但不能使 Ku 磷酸化。Lyn 与 DNA-PKcs 之间的相互作用抑制了 DNA-PKcs 的活性以及 DNA-PKcs 与 Ku/DNA 形成复合物的能力。这些结果支持了这样一种假说，即在对 DNA 损伤的反应中，Lyn 与 DNA-PKcs 之间存在功能相互作用。

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