Dephosphorylation of Cdk2 Thr160 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 (Thr160 in Cdk2) by CDK-activating kinase (CAK). Human KAP (also called Cdi1), a CDK-associated phosphatase, was shown to dephosphorylate Thr160 in human Cdk2. KAP was unable to dephosphorylate Tyr15 and only dephosphorylated Thr160 in native monomeric Cdk2. The binding of cyclin A to Cdk2 inhibited the dephosphorylation of Thr160 by KAP but did not preclude the binding of KAP to the cyclin A-Cdk2 complex. Moreover, the dephosphorylation of Thr160 by KAP prevented Cdk2 kinase activity upon subsequent association with cyclin A. These results suggest that KAP binds to Cdk2 and dephosphorylates Thr160 when the associated cyclin subunit is degraded or dissociates.
Poon
R Y
RY
Molecular Biology and Virology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037-1099, USA.
Hunter
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D000595:Amino Acid Sequence; D001483:Base Sequence; D042846:CDC2-CDC28 Kinases; D018797:Cell Cycle Proteins; D002460:Cell Line; D051357:Cyclin-Dependent Kinase 2; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism; D054637:Dual-Specificity Phosphatases; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D000095043:Cyclin-Dependent Kinase-Activating Kinase
D018797:Cell Cycle Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins; D011993:Recombinant Fusion Proteins; D013912:Threonine; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D010749:Phosphoprotein Phosphatases; C084429:CDKN3 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases; D000095043:Cyclin-Dependent Kinase-Activating Kinase