Research ArticleCell Biology

MAPK feedback encodes a switch and timer for tunable stress adaptation in yeast

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Science Signaling  13 Jan 2015:
Vol. 8, Issue 359, pp. ra5
DOI: 10.1126/scisignal.2005774

One Pathway: Both a Switch and a Rheostat

Signaling pathways can mediate responses that are on or off, like a light switch, or can mediate responses that are graded, like a dimmer switch. English et al. explored the yeast response to osmotic stress, which is mediated by a mitogen-activated protein kinase cascade involving the kinase Hog1. Using a new method for quantifying the abundance of phosphorylated Hog1, which requires dual phosphorylation for activation, this kinase exhibited switchlike activation and then produced a graded duration of activity that reflected the intensity of the osmotic stress. Positive and negative feedback from Hog1 produced these dual behaviors. Genetic analysis indicated that several upstream components of the pathway contributed to the profile of Hog1 activity. Analysis of transcriptional and translational profiles of yeast exposed to persistent osmotic stress showed that the initial response triggered adaptive changes that enabled cell survival and later transcriptional changes enabled the cells to recover.


Signaling pathways can behave as switches or rheostats, generating binary or graded responses to a given cell stimulus. We evaluated whether a single signaling pathway can simultaneously encode a switch and a rheostat. We found that the kinase Hog1 mediated a bifurcated cellular response: Activation and commitment to adaptation to osmotic stress are switchlike, whereas protein induction and the resolution of this commitment are graded. Through experimentation, bioinformatics analysis, and computational modeling, we determined that graded recovery is encoded through feedback phosphorylation and a gene induction program that is both temporally staggered and variable across the population. This switch-to-rheostat signaling mechanism represents a versatile stress adaptation system, wherein a broad range of inputs generate an “all-in” response that is later tuned to allow graded recovery of individual cells over time.

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