Molecular functions of the Ssk1 osmo-regulator in the yeast HOG MAPK pathway

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Yeast Ste11 MAPKKK takes part in three different MAPK signaling modules that respond to, respectively, mating pheromones, osmostress, and nutritional conditions. Nevertheless, each MAPK pathway is activated only by the cognate stimulus. To investigate how osmostress activates only the Hog1 MAP kinase module (HOG pathway), we isolated and characterized constitutively activated alleles in three key genes involved in the pathway, namely STE11, STE50, and SHO1. We found that Cdc42 not only activates the upstream kinases in the HOG pathway, Ste20 and Cla4, but also binds to Ste11-bound Ste50, thereby bringing activated Ste20/Cla4 and their substrate Ste11 together. Subsequently, activated Ste11 and its HOG pathway-specific substrate, Pbs2 MAPKK, are brought together by binding of the Ste50-Ste11 complex to the cytoplasmic domain of Sho1, to which Pbs2 is also bound. Thus, both Sho1 and Ste50 act as adaptive docking proteins that restrict the flow of the osmostress signal from Ste20/Cla4 to Pbs2, via Ste11.