Direct interaction of Ste11 and Mkk1/2 through Nst1 integrates high-osmolarity glycerol and pheromone pathways to the cell wall integrity MAPK pathway

Coordination and cross talks of MAPK pathways are critical for signaling efficiency, but their mechanisms are not well understood. Slt2, the MAP kinase of cell wall integrity pathway (CWI), is activated by heat stress even in the absence of upstream components of this pathway, suggesting a supplementary input for Slt2 activation. Here, we identify a new interaction of Ste11 and Mkk1, mediated by Nst1 that connects the high-osmolarity glycerol and pheromone pathways directly to CWI pathway in response to heat and pheromone. We suggest that Ser⁴⁰⁷ and Thr⁴¹¹ are novel residues of Mkk1 activated by these MAPK pathways.