Mammalian Polo-like kinase 3 (PIU) is a multifunctional protein involved in stress response pathways
Mammalian Polo-like kinase 3 (PIU) is a multifunctional protein involved in stress response pathways
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DOI：
10.1038/sj.onc.1205850
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发表时间：
2002-09-26
期刊：
影响因子：
8
通讯作者：
Stambrook, PJ
中科院分区：
文献类型：
--
作者：
Bahassi, EM;Conn, CW;Stambrook, PJ
polo样激酶（Plks）是一个保守的激酶家族，参与细胞周期调节，特别是在G2和有丝分裂中。在哺乳动物中，至少有三个Plk家族成员。在这里，我们发现Plk3是一种应激反应蛋白，在DNA损伤或有丝分裂纺锤体断裂后被磷酸化。磷酸化增强了它的激酶活性，并且依赖于前一种情况下的共济失调毛细血管扩张突变（ATM），而不是后者。Plk3与150至大于600 kDa的多种大小的配合物结合。在未磷酸化的形式下，它以约400 kDa的分子量从施胶柱中洗脱，而在磷酸化时，它与150和600 kDa的复合物结合。在与它物理结合和利用的蛋白质中，作为底物的是Chk2和P53。它磷酸化Chk2的残基与ATM的主要靶标苏氨酸68 （Thr68）不同。虽然ATM是体内磷酸化和激活Chk2所必需的，但Plk3似乎有助于其完全激活。在其磷酸化的形式下，它也与未聚合的微管蛋白分离并形成复合物。总的来说，这些数据表明，Plk3是一种多功能蛋白，与多种复合物相关，有助于应对DNA损伤和有丝分裂纺锤体断裂引起的应激，尽管途径不同。
The Polo-like kinases (Plks) are a conserved family of kinases that contribute to cell cycle regulation, particularly in G2 and mitosis. In mammals, there are at least three members of the Plk family. Here we show that Plk3 is a stress response protein that becomes phosphorylated following DNA damage or mitotic spindle disruption. Phosphorylation enhances its kinase activity and is dependent upon ataxia telangiectasia-mutated (ATM) in the former case but not the latter. Plk3 associates with complexes of multiple sizes ranging from 150 to greater then 600 kDa. In its unphosphorylated form it elutes from a sizing column at about 400 kDa whereas it associates with complexes of 150 and 600 kDa when phosphorylated. Among the proteins with which it physically associates and utilizes, as substrates are Chk2 and P53. It phosphorylates Chk2 on a residue different from threonine 68 (Thr68), the principal target for ATM. While ATM is necessary for phosphorylation and activation of Chk2 in vivo, Plk3 seems to contribute to its full activation. In its phosphorylated form it also coelutes and forms a complex with unpolymerized tubulin. In aggregate, the data argue that Plk3 is a multifunctional protein that associates with multiple complexes and that contributes to response to stress incurred by DNA damage and mitotic spindle disruption, albeit via different pathways.