A new human p34 protein kinase, CDK2, identified by complementation of a cdc28 mutation in Saccharomyces cerevisiae, is a homolog of Xenopus Eg1.
The onset of S-phase and M-phase in both Schizosaccharomyces pombe and Saccharomyces cerevisiae requires the function of the cdc2/CDC28 gene product, p34, a serine-threonine protein kinase. A human homolog, p34cdc2, was identified by functional complementation of the S.pombe cdc2 mutation (Lee and Nurse, 1987). Using a human cDNA expression library to search for suppressors of cdc28 mutations in S. cerevisiae, we have identified a second functional p34 homolog, CDK2 cell division kinase). This gene is expressed as a 2.1 kb transcript encoding a polypeptide of 298 amino acids. This protein retains nearly all of the amino acids highly conserved among previously identified p34 homologs from other species, but is considerably divergent from all previous p34cdc2 homologs, approximately 65% identity. This gene encodes the human homolog of the Xenopus Eg1 gene, sharing 89% amino acid identity, and defines a second sub-family of CDC2 homologs. A second chromosomal mutation which arose spontaneously was required to allow complementation of the cdc28-4 mutation by CDK2. This mutation blocked the ability of this strain to mate. These results suggest that the machinery controlling the human cell cycle is more complex than that for fission and budding yeast.
Elledge
S J
SJ
Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030.
Spottswood
M R
MR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D016203:CDC2 Protein Kinase / Q000235:genetics*; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D004271:DNA, Fungal; D005656:Fungal Proteins / Q000235:genetics* / Q000302:isolation & purification; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011061:Poly A / Q000032:analysis; D011494:Protein Kinases / Q000235:genetics* / Q000302:isolation & purification; D017346:Protein Serine-Threonine Kinases; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D014981:Xenopus; D029867:Xenopus Proteins
D004271:DNA, Fungal; D005656:Fungal Proteins; D012333:RNA, Messenger; D029867:Xenopus Proteins; D011061:Poly A; D012313:RNA; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495891:Cdk2 protein, Xenopus; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases