The Founding Member of the Ste20 Kinase Superfamily

Ste (from “sterile”) genes were discovered by genetic analysis of mating in the budding yeast Saccharomyces cerevisiae. Mating is mediated by the fusion of haploid yeast cells. Haploid cells identify mating partners by pheromones released from cells of the opposite mating type. These pheromones bind to membrane receptors that in turn activate G protein signaling and a downstream kinase cascade (8). Ste20 specifically was identified as a suppressor of mating defects induced by a dominant negative form of a G -subunit required for pheromone signaling (25) and as a dominant activator of the mating response (41). Biochemical characterization demonstrated that STE20 encodes a serine/threonine kinase (57). Ste20 is the founding member of a kinase superfamily that is divided into two groups, the p21-activated kinases (PAKs) and the germinal center kinases (GCKs). These two groups are subdivided further into 10 subfamilies: PAK-I and -II and GCK-I through -VIII (5) (FIGURE 1). PAKs are distinguished by the presence of a kinase domain located in the COOH terminus and an NH2-terminal p21 GTPase-binding domain that mediates binding to small GTPases such as Cdc42 and Rac. GCKs lack GTPase-binding domains, and the kinase domain is located in the NH2 terminus (FIGURE 1). Ste20-type kinases play essential roles in signaling pathways that regulate fundamental cellular processes, including cell-cycle control, apoptosis, development, cell growth, and cell stress responses (5). FIGURE 2 shows three well-defined Ste20 signaling pathways that have been identified in yeast by genetic and molecular analyses. In all three pathways, activation of Ste20 triggers a MAPK cascade. Yeast Ste20 signaling cascades control cell growth, mating, and associated cell-cycle events and the osmoregulatory response to hypertonic stress.