Cell cycle events are regulated by the sequential activation and deactivation of cyclin-dependent kinases (Cdks), including Cdk2 and Cdc2. Cdk2 in complexes with cyclin E and cyclin A appears necessary for the onset and progression of DNA replication, while the Cdc2 kinase in complexes with cyclin A or cyclin B is required for the initiation of cell division. Wee 1 has been identified as a protein kinase that suppresses the entry into mitosis by mediating inhibiting tyrosine phosphorylation of Cdc2 p34. In contrast, members of the Cdc25 family of protein phosphatases function as mitotic activators by dephosphorylation of Cdc2 p34 on regulatory tyrosine and possibly threonine residues. The Cdc25 gene family consists of at least three members that share approximately 40% identity in their most conserved carboxy-terminal sequences.