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PMID:1653904

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Citation

Tsai, LH, Harlow, E and Meyerson, M (1991) Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase. Nature 353:174-7

Abstract

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.

Links

PubMed Online version:10.1038/353174a0

Keywords

Adenovirus Early Proteins; Amino Acid Sequence; Base Sequence; CDC2-CDC28 Kinases; Cloning, Molecular; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinases; Cyclins/metabolism; Genes; Humans; Macromolecular Substances; Molecular Sequence Data; Molecular Weight; Oligonucleotides/chemistry; Oncogene Proteins, Viral/metabolism; Peptide Mapping; Polymerase Chain Reaction; Precipitin Tests; Protamine Kinase/metabolism; Protein Kinases/genetics; Protein Kinases/immunology; Protein Kinases/metabolism; Protein-Serine-Threonine Kinases; Substrate Specificity

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