STE18 encodes the gamma subunit of the heterotrimeric G-protein complex involved in the mating pathway (2). Yeast respond to mating pheromone by transducing the pheromone signal through a well-studied mitogen-activated protein kinase (MAPK) cascade (reviewed in 4, 5). The first step in the mating pathway is the binding of mating pheromone to its receptor; the pheromone receptors are encoded by STE2 in MATa cells and STE3 in MATalpha cells (6, 7). These receptors transmit their signals through a heterotrimeric G protein consisting of Gpa1p, the G-alpha subunit, Ste4p, the beta subunit, and Ste18p, the gamma subunit (8, 5, 4). After binding pheromone, the pheromone receptor undergoes a conformational change and there is an exchange of GDP for GTP on Gpa1p. In its GTP-bound form, Gpa1p has less affinity for the Ste4p-Ste18p (beta-gamma) complex, and the latter is released and able to activate downstream components of the pheromone response pathway (8, 5, 4). The beta-gamma complex binds to both the scaffolding protein Ste5p, facilitating recruitment of Ste5p and its associated kinases (Ste11p, Ste7p, and Fus3p) to the plasma membrane, and to the PAK kinase Ste20p (9, 10, 11, 12). The Ste4p-Ste18p dimer also interacts with a complex of Far1p and Cdc24p; in total, these interactions induce expression of genes involved in mating, polarization of cell growth, and ultimately cell and nuclear fusion (reviewed in 13). Cells lacking Ste18p are unable to mate (2) and do not localize Ste4p to the plasma membrane (14). Membrane association of the dimer is required for activation of the downstream pathway (10) and appears to be stabilized by dual lipid modification of Ste18p (farnesylation and palmitoylation) (3, 15).

Last updated: 2007-06-01