Distinct properties of cyclin-dependent kinase complexes containing cyclin A1 and cyclin A2.
The distinct expression patterns of the two A-type cyclins during spermatogenesis and the absolute requirement for cyclin A1 in this biological process in vivo suggest that they may confer distinct biochemical properties to their CDK partners. We therefore compared human cyclin A1- and cyclin A2-containing CDK complexes in vitro by determining kinetic constants and by examining the complexes for their ability to phosphorylate pRb and p53. Differences in biochemical activity were observed in CDK2 but not CDK1 when complexed with cyclin A1 versus cyclin A2. Further, CDK1/cyclin A1 is a better kinase complex for phosphorylating potentially physiologically relevant substrates pRb and p53 than CDK2/cyclin A2. The activity of CDKs can therefore be regulated depending upon which A-type cyclin they bind and CDK1/cyclin A1 might be preferred in vivo.
Joshi
Ayesha R
AR
Department of Gen. and Dev., Columbia University Medical Center, New York, NY 10032, USA.
Jobanputra
Vaidehi
V
Lele
Karen M
KM
Wolgemuth
Debra J
DJ
D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019925:Cyclin A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D056750:Cyclin A1; D056751:Cyclin A2; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000378:metabolism; D000077546:Roscovitine; D013379:Substrate Specificity; D013737:Testis / Q000201:enzymology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C503745:CCNA1 protein, human; C503721:CCNA2 protein, human; D019925:Cyclin A; D056750:Cyclin A1; D056751:Cyclin A2; D047428:Protein Kinase Inhibitors; D011687:Purines; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D000077546:Roscovitine; D016203:CDC2 Protein Kinase; D051357:Cyclin-Dependent Kinase 2