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Pheromoneinduced morphogenesis activates the yeast HOG MAPK pathway improving osmoadaptation capacity. Rodrigo Baltanás1, Alicia Couto2, Alan Bush1, Lucía Durrieu1, Stefan Hohmann3 and Alejandro Colman Lerner1 1 Instituto de Fisiología, Biología Molecular y Neurociencias, Consejo Nacional de Investigaciones Científicas y Técnicas y Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina. 2 CIHIDECAR-Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina. 3 Department of Cell and Molecular Biology, University of Gothenburg, Gothenburg, Sweden Environmental and internal conditions often expose cells to a multiplicity of stimuli whose consequences are difficult to predict. In addition, the complexity of MAPK signaling circuits in mammalian cells makes it difficult the understanding of how signal integratation takes place. Here we investigated the MAPK network activity of cells adapted to a high osmolarity environment in response to mating pheromone. At low osmolarity, pheromone stimulation activates two MAP kinase cascades: the pheromone response (PR) and the cell-wall integrity response (CWI). Notably, at high osmolarity, we found that the PR strongly activates a third cascade, the HOG response, in a pheromone and osmolarity dependent manner. We discovered that PR activation of HOG is not due to loss of insulation, but it is a response to a reduction in internal osmolarity, which results from an increase in glycerol release caused by PR. By analyzing single cell time courses using a clustering approach, we found that stimulation of HOG occurred in discreet transcriptional bursts that coincided with the “shmooing” morphogenetic process. Activation required the polarisome, the CWI MAPK Slt2, and the aquaglyceroporin Fps1. HOG activation results in a state of high glycerol turnover that improves adaptability to rapid changes in osmolarity. Our results show how a differentiation signal is able to recruit a second, unrelated sensory pathway, an example of network integration in unicellular organisms.