Cyclin-Stimulated Binding of Cks Proteins to Cyclin-Dependent Kinases

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Abstract
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 p34cdc2(the mitotic cdk) varies during the cell cycle in Xenopusegg extracts. We observed that binding of human CksHs2 to p34cdc2 was stimulated by cyclin B. This stimulation was dependent on the activating phosphorylation of p34cdc2 on Thr-161, which follows cyclin binding and is mediated by the cdk-activating kinase. Neither the inhibitory phosphorylations of p34cdc2 nor the catalytic activity of p34cdc2 was required for this stimulation. Stimulated binding of CksHs2 to another cdk, p33cdk2, required both cyclin A and activating phosphorylation. Our findings support recent models that suggest that Cks proteins target active forms of p34cdc2 to substrates.