Many groups are attempting to understand how the mating signal is propagated. We would like to understand how it is turned off. Our data suggest that the pheromone responsive Ga protein, Gpa1, interacts with an effector and, like other Ga proteins, transduces a signal. The Gpa1-mediated signal is an adaptive one. It inhibits the mating response and allows cells to resume cell division in the continued presence of agonist.
Adaptive mechanisms are a fundamental means of regulating signaling pathways.
Thus far, studies of adaptive mechanisms in mammalian cells have concentrated on the receptors. Although a great deal is known about receptor desensitization, downstream adaptive mechanisms are poorly understood. Using a strain of yeast whose viability depends on mutational inactivation of Gpa1-mediated adaptation, we have isolated a large number of adaptation mutants, which we are in the process of characterizing genetically. Our immediate goal is to identify the genes that act downstream of Gpa1 in the adaptive signaling pathway. Eventually, we would like to use yeast to uncover homologous signaling elements in mammalian cells.