The yeast histidine protein kinase, Sln1p, mediates phosphotransfer to tworesponse regulators, Ssk1p and Skn7p

The Saccharomyces cerevisiae Sln1 protein is a 'two-component' regulator in volved in osmotolerance. Two-component regulators are a family of signal-tr ansduction molecules with histidine kinase activity common in prokaryotes a nd recently identified in eukaryotes, Phosphorylation of Sln1p inhibits the HOG1 MAP kinase osmosensing pathway via a phosphorelay mechanism including Ypd1p and the response regulator, Ssk1p, SLN1 also activates an MCMI-depen dent reporter gene, P-lacZ, but this function is independent of Ssk1p, We p resent genetic and biochemical evidence that Skn7p is the response regulato r for this alternative Sln1p signaling pathway. Thus, the yeast Sln1 phosph orelay is actually more complex than appreciated previously; the Sln1 kinas e and Ypd1 phosphorelay intermediate regulate the activity of two distinct response regulators, Ssk1p and Skn7p, The established role of Skn7p in oxid ative stress is independent of the conserved receiver domain aspartate, D42 7, In contrast, we show that Sln1p activation of Skn7p requires phosphoryla tion of D427, The expression of TRX2, previously shown to exhibit Skn7p-dep endent oxidative-stress activation, is also regulated by the SLN1 phosphore lay functions of Skn7p, The identification of genes responsive to both clas ses of Skn7p function suggests a central role for Skn7p and the SLN1-SKN7 p athway in integrating and coordinating cellular response to various types o f environmental stress.