Elledge S J, Richman R, Hall F L, Williams R T, Lodgson N, Harper J W
Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030.
Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2907-11. doi: 10.1073/pnas.89.7.2907.
Critical cell cycle transitions are controlled by the coordinate actions of the p34cdc2 protein kinase and its regulatory subunits, cyclins. Recently we identified another human p34 homolog, cyclin-dependent kinase 2 (CDK2) by complementation of a cdc28-4 mutation in Saccharomyces cerevisiae using a lambda YES human cDNA expression library. CDK2 is 66% identical to CDC2Hs and 89% identical to the Xenopus Eg1 gene, forming a distinct subfamily of CDC2-related protein kinases. We have found that CDK2 encodes a 33-kDa cyclin A-associated protein kinase that contains phosphotyrosine, two characteristics it shares with CDC2Hs. However, we show that the subunit composition of these two protein kinase complexes can vary in different cell types, that they have different in vitro substrate preferences, and that CDK2 mRNA is observed much earlier than CDC2Hs mRNA when lymphocytes are stimulated to enter the cell cycle. We suggest that cells in different developmental or transformed states may have different mechanisms of cell cycle regulation.
关键的细胞周期转换由p34cdc2蛋白激酶及其调节亚基细胞周期蛋白的协同作用控制。最近，我们通过使用λYES人cDNA表达文库互补酿酒酵母中的cdc28-4突变，鉴定出另一种人p34同源物，细胞周期蛋白依赖性激酶2（CDK2）。CDK2与CDC2Hs的同源性为66%，与非洲爪蟾Eg1基因的同源性为89%，形成了CDC2相关蛋白激酶的一个独特亚家族。我们发现CDK2编码一种33 kDa的细胞周期蛋白A相关蛋白激酶，它含有磷酸酪氨酸，这是它与CDC2Hs共有的两个特征。然而，我们表明这两种蛋白激酶复合物的亚基组成在不同细胞类型中可能有所不同，它们在体外具有不同的底物偏好，并且当淋巴细胞被刺激进入细胞周期时，观察到CDK2 mRNA比CDC2Hs mRNA出现得早得多。我们认为处于不同发育或转化状态的细胞可能具有不同的细胞周期调节机制。
