Arias et al. BMC Genomics 2011, 12:390 http://www.biomedcentral.com/1471-2164/12/390 R E S E A R C H A R T I C L E Open Access Genome-wide survey of yeast mutations leading to activation of the yeast cell integrity MAPK pathway: Novel insights into diverse MAPK outcomes Patricia Arias, Sonia Díez-Muñiz, Raúl García, César Nombela, José M Rodríguez-Peña* and Javier Arroyo 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. Conclusion: 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. Background The capacity to respond properly to external stimuli or environmental conditions is essential for homeostasis in eukaryotes. Signaling pathways, in particular those mediated by mitogen-activated protein kinases (MAPKs), play a key role in these processes. A significant amount of research has been conducted in recent years to charac- terize these signal transduction pathways, based largely on the model yeast Saccharomyces cerevisiae (also known as baker’s or budding yeast). Since MAPK pathways are evolutionarily conserved, insights gained from yeast con- tribute to a better understanding of orthologous path- ways in higher organisms. The basic assembly of MAPK * Correspondence: josemanu@farm.ucm.es Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, IRYCIS, 28040 Madrid, Spain pathways is a three-component module conserved from yeast to humans, consisting of three kinases that establish a sequential activation pathway by means of phosphoryla- tion events [1]. The regulation of MAPK signal transduc- tion depends on a variety of mechanisms including scaffold proteins, subcellular localization of different ele- ments and the action of protein phosphatases [2]. In yeast, six MAPK cascades have been identified that mediate the response to different stimuli: (i) pheromones (pheromone response pathway); (ii) nitrogen starvation (filamentous growth pathway); (iii) hyperosmolarity (high osmolarity/glycerol pathway); (iv) STE vegetative growth pathway (SVG) [3]; (v) nutrient starvation (spore wall assembly pathway); and (vi) cell wall stress (CWI: cell wall integrity pathway) (see an extensive review of MAPK path- ways in [2]). The CWI pathway is essential for maintaining © 2011 Arias et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.