Reversible tyrosine phosphorylation and cell cycle control.

In eukaryotic organisms, reversible tyrosine phosphorylation has been established as an important element in the regulation of cell growth and more recently as an essential element in the regulation of the cell division cycle. The activity of p34cdc2, a protein kinase whose activity is required for the entry of cells into mitosis, is tightly controlled by reversible phosphorylation at tyrosine 15. A complex network of interacting protein kinases and protein phosphatases regulate the state of p34cdc2 tyrosine phosphorylation and therefore the entry of cells into mitosis. In the fission yeast Schizosaccharomyces pombe, genes encoding several of these protein kinases and protein phosphatases have been obtained through genetic approaches. In this review, we will focus on the protein kinases encoded by wee1+, mik1+ and cdr1+/nim1+ and the protein phosphatases encoded by cdc25+ and pyp1+, pyp2+ and pyp3+. Homologs of many of these regulators have been identified and characterized in higher eukaryotes underscoring the importance of reversible tyrosine phosphorylation as a universal mechanism for the regulation of the cell division cycle.