Distinct roles for cyclin-dependent kinases in cell cycle control.
The key cell-cycle regulator Cdc2 belongs to a family of cyclin-dependent kinases in higher eukaryotes. Dominant-negative mutations were used to address the requirement for kinases of this family in progression through the human cell cycle. A dominant-negative Cdc2 mutant arrested cells at the G2 to M phase transition, whereas mutants of the cyclin-dependent kinases Cdk2 and Cdk3 caused a G1 block. The mutant phenotypes were specifically rescued by the corresponding wild-type kinases. These data reveal that Cdk3, in addition to Cdc2 and Cdk2, executes a distinct and essential function in the mammalian cell cycle.
van den Heuvel
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Massachusetts General Hospital Cancer Center, Charlestown 02129.
Harlow
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D000595:Amino Acid Sequence; D016203:CDC2 Protein Kinase / Q000502:physiology; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000502:physiology*; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000502:physiology*; D005822:Genetic Vectors; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D014407:Tumor Cells, Cultured
D016213:Cyclins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases