Preferences for phosphorylation sites in the retinoblastoma protein of D-type cyclin-dependent kinases, Cdk4 and Cdk6, in vitro
Preferences for phosphorylation sites in the retinoblastoma protein of D-type cyclin-dependent kinases, Cdk4 and Cdk6, in vitro
复制标题
DOI：
10.1093/jb/mvi050
复制
发表时间：
2005-03-01
影响因子：
2.7
通讯作者：
Hirai, H
中科院分区：
文献类型：
--
作者：
Takaki, T;Fukasawa, K;Hirai, H
D 型细胞周期蛋白依赖性激酶（Cdk4 和 Cdk6）调节哺乳动物细胞周期的 G1 至 S 期进程。有人认为，Cdk4 和 Cdk6 在体内可能具有不同的功能，尽管它们在生化上无法区分。在这里，我们表明，尽管这些 Cdks 磷酸化 pRB 中的多个残基，但它们在体外具有不同的残基选择性； Thr821 和 Thr826 分别优先被 Cdk6 和 Cdk4 磷酸化。这提出了不同底物特异性导致其在细胞事件调节中发挥不同作用的可能性。此外，我们的结果表明了 Cdk 本身有助于底物识别的新概念。
D-type cyclin-dependent kinases (Cdk4 and Cdk6) regulate the G1 to S phase progression of the mammalian cell cycle. It has been suggested that Cdk4 and Cdk6 may have distinct functions in vivo, even though they are indistinguishable biochemically. Here we show that although these Cdks phosphorylate multiple residues in pRB, they do so with different residue selectivities in vitro; Thr821 and Thr826 are preferentially phosphorylated by Cdk6 and Cdk4, respectively. This raises the possibility different substrate specificities lead to their different roles in the regulation of cellular events. Furthermore, our results indicate the new concept that Cdk itself contributes to substrate recognition.