THE WIS1 SIGNAL-TRANSDUCTION PATHWAY IS REQUIRED FOR EXPRESSION OF CAMP-REPRESSED GENES IN FISSION YEAST

The wis1 protein kinase of Schizosaccharomyces pombe is a member of th e MAP kinase kinase family. Loss of wis1 function has previously been reported to lead to a delay in the G(2)-mitosis transition, loss of vi ability in stationary phase, and hypersensitivity to osmotic shock, It acts at least in part by activating the MAP kinase homologue sty1; lo ss-of-function sty1 mutants share many phenotypes with wis1 deletion m utants. We show here that, in addition, loss of wis1 function leads to defective conjugation, and to suppression of the hyperconjugation phe notype of the pat1-114 mutation, Consistent with this, the induction o f the mei2 gene, which is normally induced by nitrogen starvation, is defective in wis1 mutants, In wild-type cells, nitrogen starvation lea ds to mei2 induction through a fall in intracellular cyclic AMP (cAMP) level and activity of the cAMP-dependent protein kinase, We show here that wis1 function is required for mei2 induction following nitrogen starvation, Expression of the fbp1 gene is negatively regulated by cAM P in response to glucose limitation: induction of fbp1 also requires w is1 and sty1 function, Loss of wis1 is epistatic over increased fbp1 e xpression brought about by loss of adenylate cyclase (git2/cyr1) or cA MP-dependent protein kinase (pka1) function, These observations can be explained by a model in which the pka1 pathway negatively regulates t he wis1 pathway, or the two pathways might act independently on downst ream targets. The latter explanation is supported, at least as regards regulation of cell division, by the observation that loss of function of the regulatory subunit of the cAMP-dependent protein kinase (cgs1) brings about a modest increase in cell length at division in both wis 1(+) and wis1 Delta genetic backgrounds.