WSC, a family of genes required for the maintenance of cell wall integrity and the heat shock response in Saccharomyces cerevisiae

Cells can detect specific signaling molecules and then transduce this information across the plasma membrane into their interior where certain events occur to mount an appropriate response. The series of events that happen from the detection of the signal to a response by the cell are referred to as a signal transduction pathway. In addition cells must be able to sense environmental stresses and then react accordingly to protect themselves from damage by these stresses. Little is known about the molecular basis of the initial events of this response. It is known that mitogen-activated protein kinase (MAPK) cascades play an important role in the stress response. In yeast this MAPK cascade is regulated by the protein kinase C, PKC1, (called the PKC1-MPK1 pathway) and functions in heat shock response and in the maintenance of cell wall integrity. We have identified a novel family of proteins that are putative regulators of this pathway. WSC1, WSC2 and WSC3 (for cell w&barbelow;all integrity and s&barbelow;tress response c&barbelow;omponent) encode predicted integral membrane proteins that localize to the intracellular periphery of the cell. Genetic evidence places WSC function upstream of the PKC1-MPK1 pathway in the maintenance of cell wall integrity and in the heat shock response and suggest that WSC is involved in the activation of this pathway. We also find that WSC exerts its effects in the heat shock response through a PKC1-MPK1 independent pathway which acts parallel to the RAS-cAMP pathway on the same downstream, but with opposing results. The RAS-cAMP pathway is required for cell cycle progression and affects the heat shock response. A genetic screen to identify proteins that functionally interact with WSC lead to the isolation of MATa1. Genetic analyses suggest that MATa1 and WSC function in parallel pathways to regulate the maintenance of cell wall integrity and the heat shock response. These results indicate that WSC may play a role in a fundamental mechanism for how cells sense and respond to stress.