CELL-CYCLE CONTROL LINKED TO EXTRACELLULAR ENVIRONMENT BY MAP KINASE PATHWAY IN FISSION YEAST

IN fission yeast the onset of mitosis is brought about by Cdc2/Cdc13 kinase, which is inhibited by the Wee1/Mik1 tyrosine kinases and activated by Cdc25 tyrosine phosphatase(1). This control network integrates many signals, including those that monitor DNA replication, DNA damage and cell size, We report here that a fission yeast MAP kinase pathway links the cell-cycle G(2)/M control with changes in the extracellular environment that affect cell physiology. Fission yeast spc1(-) mutants have a G(2) delay that is greatly exacerbated by growth in high osmolarity media and nutrient limitation. A lethal interaction of spc1 and cdc25 mutations shows that Spc1 promotes the onset of mitosis, Spc1 is a MAP kinase homologue that is activated by Wis1 kinase in response to osmotic stress and nutrient limitation, Spc1 is inactivated by Pyp1, a phosphatase previously identified as a mitotic inhibitor(2,3). Pyp1 dephosphorylates only tyrosine-173 of Spc1, unlike the dual-specificity phosphatases that have been shown to regulate other MAP kinases(4).