Eukaryotic cells use multiple mitogen-activated protein kinase (MAPK) cascades to evoke appropriate responses to external stimuli. In Saccharomyces cerevisiae, the MAPK Fus3 is activated by pheromone-binding heterotrimeric guanosine triphosphate-binding protein (G protein)-coupled receptors to promote mating, whereas the MAPK Hog1 is activated by hyperosmotic stress to elicit the high-osmolarity glycerol (HOG) response. Although these MAPK pathways share several upstream components, exposure to either pheromone or osmolyte alone triggers only the appropriate response. We used fluorescence localization- and transcription-specific reporters to assess activation of these pathways in individual cells on the minute and hour time scale, respectively. Dual activation of these two MAPK pathways occurred over a broad range of stimulant concentrations and temporal regimes in wild-type cells subjected to costimulation. Thus, signaling specificity is achieved through an "insulation" mechanism, not a "cross-inhibition" mechanism. Furthermore, we showed that there was a critical period during which Hog1 activity had to occur for proper insulation of the HOG pathway.

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Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't

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Patterson JC, Klimenko ES, Thorner J

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