title: Genome-wide survey of yeast mutations leading to activation of the yeast cell integrity MAPK pathway: novel insights into diverse MAPK outcomes.
abstract: BACKGROUND
  The yeast cell wall integrity mitogen-activated protein kinase (CWI-MAPK) pathway is the main regulator of adaptation responses to cell wall stress in yeast. Here, we adopt a genomic approach to shed light on two aspects that are only partially understood, namely, the characterization of the gene functional catalog associated with CWI pathway activation and the extent to which MAPK activation correlates with transcriptional outcomes.
  
  
  RESULTS
  A systematic yeast mutant deletion library was screened for constitutive transcriptional activation of the CWI-related reporter gene MLP1. Monitoring phospho-Slt2/Mpk1 levels in the identified mutants revealed sixty-four deletants with high levels of phosphorylation of this MAPK, including mainly genes related to cell wall construction and morphogenesis, signaling, and those with unknown function. Phenotypic analysis of the last group of mutants suggests their involvement in cell wall homeostasis. A good correlation between levels of Slt2 phosphorylation and the magnitude of the transcriptional response was found in most cases. However, the expression of CWI pathway-related genes was enhanced in some mutants in the absence of significant Slt2 phosphorylation, despite the fact that functional MAPK signaling through the pathway was required. CWI pathway activation was associated to increased deposition of chitin in the cell wall - a known survival compensatory mechanism - in about 30% of the mutants identified.
  
  
  CONCLUSIONS
  We provide new insights into yeast genes related to the CWI pathway and into how the state of activation of the Slt2 MAPK leads to different outcomes, discovering the versatility of this kind of signaling pathways. These findings potentially have broad implications for understanding the functioning of other eukaryotic MAPKs.
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, IRYCIS, 28040 Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Arias
authors.forename: Sonia
authors.initials: S
authors.lastname: Díez-Muñiz
authors.forename: Raúl
authors.initials: R
authors.lastname: García
authors.forename: César
authors.initials: C
authors.lastname: Nombela
authors.forename: José M
authors.initials: JM
authors.lastname: Rodríguez-Peña
authors.forename: Javier
authors.initials: J
authors.lastname: Arroyo
mesh_terms: D002473:Cell Wall / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D002686:Chitin / Q000378:metabolism; D025141:Drug Resistance, Fungal / Q000235:genetics; D017353:Gene Deletion; D016681:Genome, Fungal / Q000235:genetics; D023281:Genomics; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013309:Streptothricins / Q000494:pharmacology; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D002686:Chitin; D013309:Streptothricins; D020928:Mitogen-Activated Protein Kinases; C072724:SLT2 protein, S cerevisiae