Mutations in WSC genes for putative stress receptors result in sensitivityto multiple stress conditions and impairment of Rlm1-dependent gene expression in Saccharomyces cerevisiae

Intracellular signaling by mitogen-activated protein (MAP) kinase cascades plays an essential role in the cellular response to environmental stress. I n the yeast Saccharomyces cerevisiae. the PKC1-regulated, stress-activated MAP kinase pathway, the MPK1 cascade, is activated by heat and by a decreas e in osmolarity. The genes WSC1. WSC2 and WSC3 encode putative receptors th at maintain cell wall integrity under conditions of heat stress. Genetic st udies place the function of the WSC genes upstream of the MPK1 kinase casca de. To further define the role of the WSC family in the stress response we determined whether: (1) the wsc Delta mutants are sensitive to other enviro nmental stress conditions, in addition to heat shock: (2) expression from f our transcriptional control elements, known to be activated by stress, is i mpaired in wsc Delta mutants; and (3) Wsc4, a Wsc homolog, has functions th at overlap with those of the other Wsc family members. We report here that deletion of WSC and PKC1 causes hypersensitivity to ethanol, hydrogen perox ide and DNA-damaging drugs. In wsc Delta mutants expression of beta -galact osidase from the AP-1 response element (ARE), the heat shock response eleme nt (HSE) or the stress response element (STRE) is not reduced. In contrast. expression of a reporter gene placed under the control of the Rlm1 (transc ription factor)-dependent response element is significantly reduced in wsc Delta mutants. This suggests that the lysis defect of wsc Delta mutants is at least in part caused by a defect in transcriptional regulation by Rlm1. Phenotypic analysis of the effect of deleting WSC4 in a wsc1 Delta mutant s how that. unlike WSC2 or WSC3, deletion of WSC4 does not exacerbate the lys is defect of a wsc1 Delta strain. In contrast, deletion of WSC4 enhances th e sensitivity of the wsc1 Delta mutant to heat shock, ethanol, and a DNA-da maging drug, suggesting that WSC4 plays a role in the response to environme ntal stress but that its function may differ from those of the other WSC fa mily members.