Binding of HTm4 to cyclin-dependent kinase (cdk)-associated phosphatase (KAP)•cdk2•cyclin A complex enhances the phosphatase activity of KAP, dissociates cyclin A, and facilitates KAP dephosphorylation of cdk2

Cyclin-dependent kinase 2 (cdk2) activation requires phosphorylation of Thr(160) and dissociation from cyclin A. The T-loop of cdk2 contains a regulatory phosphorylation site at Thr(160). An interaction between cdc-associated phosphatase (KAP) and cdk2 compromises the interaction between cdk2 and cyclin A, which permits access of KAP, a Thr(160)-directed phosphatase, to its substrate, cdk2. We have reported that KAP is bound and activated by a nuclear membrane protein, HTm4. Here, we present in vitro data showing the direct interaction between the HTm4 C terminus and KAP Tyr(141). We show that this interaction not only facilitates access of KAP to Thr(160) and accelerates KAP kinetics, but also forces exclusion of cyclin A from the KAP.cdk2 complex.