cdc2 Protein Kinase: Interactions with Cyclins and

The cdc2 protein is an essential switch for cell cycle progression i all eukaryotic ells. Originally identified through genetic analysis of division mutants of Schizosaccharomyces pombe and Saccharomyces cere-visiae (where the cdc2 homolog is called CDC28), the cdc2 gene function is needed at two control points, in late G 1 and in G 2 before mitosis (for review, see Nor-bury and Nurse 1991; Reed 1991). Several genes encoding proteins sharing structural features with cdc2 have been identified. For some of these related proteins, a functional homology with cdc2/28 of yeast was found. In particular, the human homolog of cdc2 was identified for its ability to fully rescue a yeast strain carrying a temperature-sensitive allele of cdc2 (Lee and Nurse 1987). In other cases, genes encoding proteins with high similarity to cdc2 at the amino acid level were not able to rescue cdc2/28 mutations (Lehner and O'Farrell 1990; Paris et al. 1991). It is not known whether these proteins also play a role in cell cycle regulation. The cdc2 catalytic subunit shares the features of known serine/threonine protein kinases (Draetta 1990). Although its kinase activity varies during the cell cycle (Draetta and Beach 1988; Booher et al. 1989; Draetta et al. 1989), the total levels of cdc2 are con-stant in somatic ells (Simanis and Nurse 1986; Draetta and Beach 1988) as well as during the highly synchro-nous divisions of early embryonic ells (Draetta et al. 1989). In fact, the periodic activation of cdc2 is reg-ulated by phosphorylation events and reversible as-sociation with regulatory subunits. For example, in human cells, cdc2 is phosphorylated on serine, threonine, and tyrosine residues (Draetta et al. 1988) and associates with at least hree other proteins, asmall protein homologous to the S. pombe sucl (Draetta et al. 1987; Draetta nd Beach 1988), a M r 62,000 protein, now known to be the human homolog of cyclin