title: Suppressors of an adenylate cyclase deletion in the fission yeast Schizosaccharomyces pombe.
abstract: Schizosaccharomyces pombe utilizes two opposing signaling pathways to sense and respond to its nutritional environment. Glucose detection triggers a cyclic AMP signal to activate protein kinase A (PKA), while glucose or nitrogen starvation activates the Spc1/Sty1 stress-activated protein kinase (SAPK). One process controlled by these pathways is fbp1+ transcription, which is glucose repressed. In this study, we isolated strains carrying mutations that reduce high-level fbp1+ transcription conferred by the loss of adenylate cyclase (git2delta), including both wis1- (SAPK kinase) and spc1- (SAPK) mutants. While characterizing the git2delta suppressor strains, we found that the git2delta parental strains are KCl sensitive, though not osmotically sensitive. Of 102 git2delta suppressor strains, 17 strains display KCl-resistant growth and comprise a single linkage group, carrying mutations in the cgs1+ PKA regulatory subunit gene. Surprisingly, some of these mutants are mostly wild type for mating and stationary-phase viability, unlike the previously characterized cgs1-1 mutant, while showing a significant defect in fbp1-lacZ expression. Thus, certain cgs1- mutant alleles dramatically affect some PKA-regulated processes while having little effect on others. We demonstrate that the PKA and SAPK pathways regulate both cgs1+ and pka1+ transcription, providing a mechanism for cross talk between these two antagonistically acting pathways and feedback regulation of the PKA pathway. Finally, strains defective in both the PKA and SAPK pathways display transcriptional regulation of cgs1+ and pka1+, suggesting the presence of a third glucose-responsive signaling pathway.
authors.affiliation: Biology Department, Boston College, Chestnut Hill, MA 02467, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Stiefel
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: David A
authors.initials: DA
authors.lastname: Kelly
authors.forename: Rozmin T K
authors.initials: RT
authors.lastname: Janoo
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Seitz
authors.forename: Simon K
authors.initials: SK
authors.lastname: Whitehall
authors.forename: Charles S
authors.initials: CS
authors.lastname: Hoffman
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D017384:Sequence Deletion; D015398:Signal Transduction
chemical_list: D029702:Schizosaccharomyces pombe Proteins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D048670:MAP Kinase Kinase 4; D000262:Adenylyl Cyclases; D005947:Glucose