Cyclin-stimulated binding of Cks proteins to cyclin-dependent kinases
Cyclin-stimulated binding of Cks proteins to cyclin-dependent kinases
复制标题
DOI：
10.1128/mcb.18.7.3659
复制
发表时间：
1998-07-01
影响因子：
5.3
通讯作者：
Solomon, MJ
中科院分区：
文献类型：
--
作者：
Egan, EA;Solomon, MJ
尽管Cks蛋白是第一个被发现的周期蛋白依赖性蛋白激酶（cdks）的结合伙伴，但它们的细胞周期功能仍不清楚。为了帮助阐明Cks蛋白的功能，我们在爪蟾卵提取物中检测了它们与p34(cdc2)（有丝分裂cdk）的结合是否在细胞周期中发生变化。我们观察到细胞周期蛋白b刺激了人类CksHs2与p34（cdc2）的结合，这种刺激依赖于Thr-161上p34（cdc2）的活化磷酸化，这是在细胞周期蛋白结合之后，由cdk活化激酶介导的。这种刺激既不需要p34（cdc2）的抑制性磷酸化，也不需要p34（cdc2）的催化活性。刺激CksHs2与另一个cdk p33（cdk2）结合，需要细胞周期蛋白A和激活磷酸化。我们的发现支持最近的模型，表明Cks蛋白靶向活性形式的p34（cdc2）到底物。
Although Cks proteins were the first identified binding partners of cyclin-dependent protein kinases (cdks), their cell cycle functions have remained unclear. To help elucidate the function of Cks proteins, we examined whether their binding to p34(cdc2) (the mitotic cdk) varies during the cell cycle in Xenopus egg extracts. We observed that binding of human CksHs2 to p34(cdc2) was stimulated by cyclin B. This stimulation was dependent on the activating phosphorylation of p34(cdc2) On Thr-161, Which follows cyclin binding and is mediated by the cdk-activating kinase. Neither the inhibitory phosphorylations of p34(cdc2) nor the catalytic activity of p34(cdc2) was required for this stimulation. Stimulated binding of CksHs2 to another cdk, p33(cdk2), required both cyclin A and activating phosphorylation. Our findings support recent models that suggest that Cks proteins target active forms of p34(cdc2) to substrates.