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Cyclin-dependent kinase 2 (Cdk2) is a member of a family of cdc2-related cell cycle protein kinases. Cdk2 shares 60% identity with cdc2 and its activity is regulated by phosphorylation in a similar fashion. Cdk2 is expressed earlier in the cell cycle than is cdc2. Like p34 [cdc2], p33 [cdk2] associates with Cyclin A in human cells. However, kinase activity associated with Cyclin A-Cdk2 is present in S phase, whereas, the kinase activity associated with Cyclin A-cdc2 is found only in G2. Cdk2 can also complex with cyclins E, D1, and D3. It is not known if the D cyclins can form active complexes with Cdk2. Cyclin E-Cdk2 kinase is active in the G1 and S phases of the cell cycle and is important (as is Cyclin A-Cdk2) for the progression from G1 to S phase. The levels of Cyclin A-Cdk2 are maximal at the G1/S transition and both Cdk2 and Cyclin A associate with DNA in the initiation complex during replication. The Rb protein has been identified as a substrate for Cdk2-Cyclin E and/or Cdk2-Cyclin A in vivo. This observation is supported by further evidence which shows that Cdk2 is activated and specifically localized to the nucleus during late G1, S phase, and G2.
