Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase.
Cyclins are regulatory subunits which associate with kinases to form complexes that control many of the important steps in cell-cycle progression. The best characterized of the cyclin-containing complexes is the association of cyclin B with the p34cdc2 kinase. The p34cdc2/cyclin B complex is required for the G2 to M transition (see refs 1-4 for review), but the physiological role of other cyclin complexes is unclear. Human cyclin A binds independently to two kinases, associating with either p34cdc2 or a related protein, p33 (refs 5-7). In adenovirus-transformed cells, the viral E1A oncoprotein seems to associate with p33/cyclin A but not with p34cdc2/cyclin A (B. Faha, M.M., L-H.T. and E.H., manuscript submitted). To isolate the gene for p33, we have cloned several novel human cdc2-related genes. The protein product of one of these genes, cdk2 (cyclin-dependent kinase 2), shares 65% sequence identity with p34cdc2 (ref. 8) and 89% identity with the Xenopus Eg-1 gene product. Immunochemical characterization and partial proteolytic mapping show that the cdk2 gene product is the cyclin A-associated p33. Immunoprecipitations of the p33cdk2 protein suggest that it can act as a protein kinase in vitro. As p33cdk2 is bound to cyclin A and is targeted by the viral E1A protein, we suggest that the p33cdk2/cyclin A complex has a unique role in cell-cycle regulation of vertebrate cells.
Tsai
L H
LH
Massachusetts General Hospital Cancer Center, Charlestown 02129.
Harlow
E
E
Meyerson
M
M
D017456:Adenovirus Early Proteins; D000595:Amino Acid Sequence; D001483:Base Sequence; D042846:CDC2-CDC28 Kinases; D003001:Cloning, Molecular; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000378:metabolism*; D005796:Genes; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009841:Oligonucleotides / Q000737:chemistry; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D010449:Peptide Mapping; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D006656:Protamine Kinase / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D013379:Substrate Specificity
D017456:Adenovirus Early Proteins; D016213:Cyclins; D046911:Macromolecular Substances; D009841:Oligonucleotides; D009856:Oncogene Proteins, Viral; D011494:Protein Kinases; D006656:Protamine Kinase; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases