Dynamic Signaling in the Hog1 MAPK Pathway Relies on High Basal Signal Transduction

High intrinsic basal signaling in mitogen-activated protein kinase pathways ensures proper dynamic responses to environmental stimuli. Intrinsically Responsive Macia et al. found that when the activity of the mitogen-activated protein kinase (MAPK), Hog1, was inhibited, the phosphorylated form of this MAPK accumulated, suggesting that signaling occurs even in the absence of stress. The basal signaling was found to be held in check by a negative feedback loop that required the kinase activity of Hog1. A model of the system that included the basal signal and the negative feedback recapitulated the experimental data and suggested that intrinsic basal signaling poises the system to respond rapidly even to small changes in osmolarity. A similar basal activity was also detected for two additional yeast MAPKs, those involved in the pheromone response, suggesting that high basal signaling may be a common property of MAPK pathways. Appropriate regulation of the Hog1 mitogen-activated protein kinase (MAPK) pathway is essential for cells to survive osmotic stress. Here, we show that the two sensing mechanisms upstream of Hog1 display different signaling properties. The Sho1 branch is an inducible nonbasal system, whereas the Sln1 branch shows high basal signaling that is restricted by a MAPK-mediated feedback mechanism. A two-dimensional mathematical model of the Snl1 branch, including high basal signaling and a Hog1-regulated negative feedback, shows that a system with basal signaling exhibits higher efficiency, with faster response times and higher sensitivity to variations in external signals, than would systems without basal signaling. Analysis of two other yeast MAPK pathways, the Fus3 and Kss1 signaling pathways, indicates that high intrinsic basal signaling may be a general property of MAPK pathways allowing rapid and sensitive responses to environmental changes.