COMMENTARY Regulation of p34 protein kinase: new insights into protein phosphorylation and the cell cycle

The reversible phosphorylation of specific residues on proteins is a ubiquitous mechanism for the regulation of cellular processes. Recently there has been a tremendous expansion of interest in the role of protein phosphorylation in the eukaryotic cell cycle. This has been a consequence of the discovery that the cdc2 gene in the fission yeast Schizosaccharomyces pombe, which is required at the onset of mitosis and also at the 'start' control point at the Gi/S transition, encodes a 34kDa protein-serine/ threonine kinase catalytic subunit (p34). Homologous genes have been identified in Saccharomyces cerevisiae (CDC28) and in all other eukaryotes examined. p34 is a component of MPF (maturationor M-phase promoting factor), and it is now apparent that p34 protein kinase is central to the control mechanism of the cell cycle in all eukaryotic cells (reviewed by Nurse, 1990). The mitotic function of p34 protein kinase has been somewhat better characterized than its role at 'start'. At the G2/M transition, p34 protein kinase is specifically and dramatically activated, and catalyses the phosphorylation of key proteins (reviewed by Moreno and Nurse, 1990; Pines and Hunter, 19906) to bring about the cellular changes that occur in mitosis. The level of p34 protein is constant throughout the cell cycle, and its protein kinase activity (usually assayed in vitro using histone HI as substrate) requires the association of p34 with cyclins, proteins that are synthesised and degraded in a cell cycle-dependent manner (Evans et al. 1983). Activation also involves a complex series of phosphorylation/ dephosphorylation events catalysed by a network of protein kinases and protein phosphatases. Although the picture is still incomplete, important developments have occurred recently in our understanding of these molecular events. Some of the protein kinases and protein phosphatases involved in controlling the phosphorylation of p34 itself have been tentatively identified and found to recognise both serine/threonine and tyrosine residues. This unexpected finding calls for a revision of our previous assumptions about the substrate specificity of such enzymes. In fact, the study of the cell cycle is now yielding new insights into the intricate mechanisms by which protein phosphorylation provides molecular switches and precise temporal control of cellular processes.