Phosphorelay system of the HOG pathway. A phosphorelay system consisting of three proteins, Sln1, Ypd1, and Ssk1, activates the HOG pathway. Sln1, the osmosensor, contains both a histidine kinase domain (black rectangle) and a receiver domain at its C terminus (hatched rectangle). Upon signal sensing, Sln1 autophosphorylates His576. Ssk1 contains a receiver domain (hatched rectangle) and is the activator of the MAPKKKs Ssk2 and Ssk22. Arrows indicate direction of phosphotransfer. Mutation of the His or Asp residues blocks phosphotransfer and results in constitutive activation of the pathway, suggesting that phosphorylation prevents activation of the HOG MAPK cascade. See the text for other details.