Cyclin-stimulated binding of Cks proteins to cyclin-dependent kinases.
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 p34(cdc2) (the mitotic cdk) varies during the cell cycle in Xenopus egg extracts. We observed that binding of human CksHs2 to p34(cdc2) was stimulated by cyclin B. This stimulation was dependent on the activating phosphorylation of p34(cdc2) on Thr-161, which follows cyclin binding and is mediated by the cdk-activating kinase. Neither the inhibitory phosphorylations of p34(cdc2) nor the catalytic activity of p34(cdc2) was required for this stimulation. Stimulated binding of CksHs2 to another cdk, p33(cdk2), required both cyclin A and activating phosphorylation. Our findings support recent models that suggest that Cks proteins target active forms of p34(cdc2) to substrates.
Egan
E A
EA
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520-8024, USA.
Solomon
M J
MJ
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D019925:Cyclin A / Q000378:metabolism*; D019926:Cyclin B / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D014981:Xenopus; D029867:Xenopus Proteins; D000095043:Cyclin-Dependent Kinase-Activating Kinase
C093090:CKS1B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019925:Cyclin A; D019926:Cyclin B; D011993:Recombinant Fusion Proteins; D029867:Xenopus Proteins; D013912:Threonine; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C083689:CKS2 protein, human; C495891:Cdk2 protein, Xenopus; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase