Dephosphorylation of Cdk2 Thr 160 by the Cyclin-Dependent Kinase-Interacting Phosphatase KAP in the Absence of Cyclin

The activation of cyclin-dependent kinases (CDKs) requires the phosphorylation of a conserved threonine (Thr 160 in Cdk2) by CDK-activating kinase (CAK). Human KAP (also called Cdi1), a CDK-associated phosphatase, was shown to dephosphorylate Thr 160 in human Cdk2. KAP was unable to dephosphorylate Tyr 15 and only dephosphorylated Thr 160 in native monomeric Cdk2. The binding of cyclin A to Cdk2 inhibited the dephosphorylation of Thr 160 by KAP but did not preclude the binding of KAP to the cyclin A-Cdk2 complex. Moreover, the dephosphorylation of Thr 160 by KAP prevented Cdk2 kinase activity upon subsequent association with cyclin A. These results suggest that KAP binds to Cdk2 and dephosphorylates Thr 160 when the associated cyclin subunit is degraded or dissociates.