title: Systematic epistasis analysis of the contributions of protein kinase A- and mitogen-activated protein kinase-dependent signaling to nutrient limitation-evoked responses in the yeast Saccharomyces cerevisiae.
abstract: Cellular responses to environmental stimuli require conserved signal transduction pathways. In budding yeast (Saccharomyces cerevisiae), nutrient limitation induces morphological changes that depend on the protein kinase A (PKA) pathway and the Kss1 mitogen-activated protein kinase (MAPK) pathway. It was unclear to what extent and at what level there is synergy between these two distinct signaling modalities. We took a systematic genetic approach to clarify the relationship between these inputs. We performed comprehensive epistasis analysis of mutants lacking different combinations of all relevant pathway components. We found that these two pathways contribute additively to nutrient limitation-induced haploid invasive growth. Moreover, full derepression of either pathway rendered it individually sufficient for invasive growth and thus, normally, both are required only because neither is maximally active. Furthermore, in haploids, the MAPK pathway contributes more strongly than the PKA pathway to cell elongation and adhesion, whereas nutrient limitation-induced unipolar budding is independent of both pathways. In contrast, in diploids, upon nutrient limitation the MAPK pathway regulates cell elongation, the PKA pathway regulates unipolar budding, and both regulate cell adhesion. Thus, although there are similarities between haploids and diploids, cell type-specific differences clearly alter the balance of the signaling inputs required to elicit the various nutrient limitation-evoked cellular behaviors.
authors.affiliation: Division of Biochemistry and Molecular Biology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3202, USA.
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Chen
authors.forename: Jeremy
authors.initials: J
authors.lastname: Thorner
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004843:Epistasis, Genetic / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D015151:Immunoblotting; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013549:Sweetening Agents / Q000494:pharmacology
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D013549:Sweetening Agents; D017868:Cyclic AMP-Dependent Protein Kinases; C541984:KSS1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose