周期蛋白 G 相关激酶通过磷酸化其 B'γ 亚基调节蛋白磷酸酶 2A。
Cyclin G-associated kinase regulates protein phosphatase 2A by phosphorylation of its B'γ subunit.
机构信息
Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, Suita City, Osaka, Japan.
出版信息
Cell Cycle. 2012 Feb 1;11(3):604-16. doi: 10.4161/cc.11.3.19114.
Protein phosphatase 2A (PP2A) bearing the B'γ (=B'α/B56γ1/PR61γ) subunit is recruited to dephosphorylation targets by cyclin G. We demonstrate here that cyclin G-associated kinase (GAK), a component of the GAK/B'γ/cyclin G complex, directly phosphorylates the B'γ-Thr104 residue and regulates PP2A activity. Indeed, an anti-B'γ-pT104 antibody detected immunofluorescence signals at the chromosome and centrosome during mitosis; these signals were reduced by siRNA-mediated GAK knockdown. After DNA damage by γ-irradiation, the chromosome signals formed foci that colocalized with a DNA double-strand break (DSB) marker H2AX-pS139 (γH2AX) and CHK2-pT68. Moreover, B'γ-pT104 enhanced PP2A holoenzyme assembly and PP2A activity, as shown by the results of an in vitro phosphatase assay. These results suggest a novel role for GAK as a regulator of dephosphorylation events under the control of the PP2A B'γ subunit.
蛋白磷酸酶 2A（PP2A）结合 B'γ（=B'α/B56γ1/PR61γ）亚基，通过细胞周期蛋白 G 被募集到去磷酸化靶标。我们在这里证明，细胞周期蛋白 G 相关激酶（GAK），GAK/B'γ/细胞周期蛋白 G 复合物的一个组成部分，直接磷酸化 B'γ-Thr104 残基并调节 PP2A 活性。事实上，一种抗 B'γ-pT104 抗体在有丝分裂过程中检测到染色体和中心体的免疫荧光信号；这些信号通过 siRNA 介导的 GAK 敲低而减少。在 γ 射线照射引起 DNA 损伤后，染色体信号形成焦点，与 DNA 双链断裂（DSB）标记物 H2AX-pS139（γH2AX）和 CHK2-pT68 共定位。此外，B'γ-pT104 增强了 PP2A 全酶组装和 PP2A 活性，如体外磷酸酶测定结果所示。这些结果表明 GAK 作为受 PP2A B'γ 亚基控制的去磷酸化事件的调节剂具有新的作用。
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