Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase

Nature. 1991 Sep 12;353(6340):174-7. doi: 10.1038/353174a0.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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

Substances

  • Adenovirus Early Proteins
  • Cyclins
  • Macromolecular Substances
  • Oligonucleotides
  • Oncogene Proteins, Viral
  • Protein Kinases
  • Protamine Kinase
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases