Nature, Vol.371, No.6494, 254-257, 1994
A Cyclin Associated with the Cdk-Activating Kinase Mo15
THE eukaryotic cell cycle is regulated by the sequential activation of cyclin-dependent kinases (CDKs)(1). CDK activation is dependent on cyclin binding(2-4) and phosphorylation of a conserved threonine (T161 in Cdc2)(5-9) mediated by the CDK-activating kinase CAK(9). A CDK-related kinase, MO15 (ref. 10), has been identified as the catalytic submit of CAK (refs 11-13). Here we use a yeast two-hybrid screen to show that a new human cyclin (cyclin H) is a MO15-associated protein. Cyclin H is a major MO15 partner in vivo and enhances the kinase activity of MO15 towards Cdk2/cyclin A. These findings demonstrate that a cyclin/kinase complex can function as a regulator of other cyclin/kinase complexes, and suggest that cyclin/kinase cascades may exist.
Keywords:PROTEIN-KINASE;CATALYTIC SUBUNIT;CELL-CYCLE;PHOSPHORYLATION;P34CDC2;CDC2;P40(MO15);P34(CDC2);INVITRO;YEAST