Figure 7.

Regulation of the Sty1p MAP kinase cascade by a two-component peroxide receptor. We propose that peroxide stress regulates the activity of a Mak2p/Mak3p histidine kinase heterodimer to control Sty1p activity. According to this model, activation of the Mak2p/Mak3p kinase via alterations in the PAS/PAC domain leads to sequential phosphorylation of histidine 221 in Mpr1p and aspartate 412 in Mcs4p. Mcs4p interacts directly with the N terminus of the Wak1p MAPKKK both before and after stress stimulation. Phosphorylation of Mcs4p alters the activity of Wak1p (and probably also the Win1p MAPKKK), leading to sequential phosphorylation of the Wis1p MAPKK and Sty1p MAPK. Other stresses control the activity of Wak1p and Win1p by an as-yet-unidentified mechanism(s).