GAK is phosphorylated by c-Src and translocated from the centrosome to chromatin at the end of telophase.
GAK is phosphorylated by c-Src and translocated from the centrosome to chromatin at the end of telophase.
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GAK 被 c-Src 磷酸化，并在末期末从中心体转移到染色质。
DOI：
10.1080/15384101.2016.1241916
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发表时间：
2017
期刊：
影响因子：
4.3
通讯作者：
Nojima H.
中科院分区：
文献类型：
--
作者：
Fukushima K;Wang M;Naito Y;Uchihashi T;Kato Y;Mukai S;Yabuta N;Nojima H.
细胞周期蛋白G相关激酶（GAK）具有c-Src的磷酸化基序（Y 412），然而，其生理意义仍然难以捉摸。在这里，我们表明，GAK磷酸化的c-Src不仅在Y 412，而且在Y1149。抗GAK-pY 412抗体识别M期GAK的移动带。免疫荧光（IF）显示GAK-pY 412/pY 1149信号在间期出现在细胞核中，在前期和前中期转移到染色体上，中期转移到中心体上，最后在核膜形成基本完成的末期转移到染色体上。GAK的这些亚细胞运动类似于DNA许可因子。事实上，质谱鉴定了微型染色体维持（MCM）3，DNA许可系统的重要组成部分，作为GAK的关联伙伴之一;免疫沉淀介导的蛋白质印迹证实了它们在体内的关联。这些结果表明，c-Src_GAK_MCM轴通过控制DNA复制许可系统在细胞周期进程中起着重要作用。
Cyclin G-associated kinase (GAK) harbors a consensus phosphorylation motif (Y412) for c-Src; however, its physiological significance remains elusive. Here, we show that GAK is phosphorylated by c-Src not only at Y412 but also at Y1149. An anti-GAK-pY412 antibody recognized the shifted band of GAK during M phase. Immunofluorescence (IF) showed that GAK-pY412/pY1149 signals were present in the nucleus during interphase, translocated to chromosomes at prophase and prometaphase, moved to centrosomes at metaphase, and finally translocated to chromosomes at the end of telophase, when nuclear membrane formation was almost complete. These subcellular movements of GAK resemble those of DNA licensing factors. Indeed, mass spectrometry identified mini-chromosome maintenance (MCM) 3, an essential component of the DNA licensing system, as one of the association partners of GAK; immunoprecipitation-mediated Western blotting confirmed their associationin vivo. These results suggest that the c-Src_GAK_MCM axis plays an important role in cell cycle progression through control of the DNA replication licensing system.