title: Global regulation of a differentiation MAPK pathway in yeast.
abstract: Cell differentiation requires different pathways to act in concert to produce a specialized cell type. The budding yeast Saccharomyces cerevisiae undergoes filamentous growth in response to nutrient limitation. Differentiation to the filamentous cell type requires multiple signaling pathways, including a mitogen-activated protein kinase (MAPK) pathway. To identify new regulators of the filamentous growth MAPK pathway, a genetic screen was performed with a collection of 4072 nonessential deletion mutants constructed in the filamentous (Σ1278b) strain background. The screen, in combination with directed gene-deletion analysis, uncovered 97 new regulators of the filamentous growth MAPK pathway comprising 40% of the major regulators of filamentous growth. Functional classification extended known connections to the pathway and identified new connections. One function for the extensive regulatory network was to adjust the activity of the filamentous growth MAPK pathway to the activity of other pathways that regulate the response. In support of this idea, an unregulated filamentous growth MAPK pathway led to an uncoordinated response. Many of the pathways that regulate filamentous growth also regulated each other's targets, which brings to light an integrated signaling network that regulates the differentiation response. The regulatory network characterized here provides a template for understanding MAPK-dependent differentiation that may extend to other systems, including fungal pathogens and metazoans.
authors.affiliation: Department of Biological Sciences, State University of New York, Buffalo, New York 14260-1300.
authors.forename: Colin A
authors.initials: CA
authors.lastname: Chavel
authors.affiliation: Department of Biological Sciences, State University of New York, Buffalo, New York 14260-1300.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Caccamise
authors.affiliation: Department of Biological Sciences, State University of New York, Buffalo, New York 14260-1300.
authors.forename: Boyang
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Biological Sciences, State University of New York, Buffalo, New York 14260-1300 pjcullen@buffalo.edu.
authors.forename: Paul J
authors.identifier: http://orcid.org/0000-0002-6703-1480
authors.initials: PJ
authors.lastname: Cullen
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D056726:Genetic Association Studies; D020935:MAP Kinase Signaling System / Q000235:genetics*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D009024:Morphogenesis; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development
chemical_list: D020928:Mitogen-Activated Protein Kinases
keywords: network hubs; response coordination; signal coordination; signal integration; signal transduction