IN the budding yeast Saccharomyces cerevisiae, the process of conjugat
ion of haploid cells of genotype MAT alpha and MAT alpha to form MAT a
lpha/alpha diploids is triggered by pheromones produced by each mating
type. These pheromones stimulate a cellular response by interaction w
ith receptors linked to a heterotrimeric G protein. Although genetic a
nalysis indicates that the pheromone signal is transmitted through the
G beta gamma dimer, the initial target(s) of G protein activation rem
ain to be determined. Temperature-sensitive cells with mutations of th
e CDC24 and CDC42 genes, which are incapable of budding and of generat
ing cell polarity at the restrictive temperature(1-3), are also unable
to mate(4). Cdc24 acts as a guanylyl-nucleotide-exchange factor for t
he Rho-type GTPase Cdc42(5), which has been shown to be a fundamental
component of the molecular machinery controlling morphogenesis in euka
ryotic cells(6-10). Therefore, the inability of cdc24 and cdc42 mutant
s to mate has been presumed to be due to a requirement for generation
of cell polarity and related morphogenetic events during conjugation,
But here we show that Cdc42 has a direct signalling role in the mating
-pheromone response between the G protein and the downstream protein k
inase cascade.