The cellular ability to react to environmental fluctuations depends on signaling networks that are controlled by the dynamic activities of kinases and phosphatases. Here, to gain insight into these stress-responsive phosphorylation networks, we generated a quantitative mass spectrometry-based atlas of early phosphoproteomic responses in Saccharomyces cerevisiae exposed to 101 environmental and chemical perturbations. We report phosphosites on 59% of the yeast proteome, with 18% of the proteome harboring a phosphosite that is regulated within 5 min of stress exposure. We identify shared and perturbation-specific stress response programs, uncover loss of phosphorylation as an integral early event, and dissect the interconnected regulatory landscape of kinase-substrate networks, as we exemplify with target of rapamycin signaling. We further reveal functional organization principles of the stress-responsive phosphoproteome based on phosphorylation site motifs, kinase activities, subcellular localizations, shared functions and pathway intersections. This information-rich map of 25,000 regulated phosphosites advances our understanding of signaling networks.

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Journal Article

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Leutert M, Barente AS, Fukuda NK, Rodriguez-Mias RA, Villén J

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