Signal transduction by a nondissociable heterotrimeric yeast G protein

Many signal transduction pathways involve heterotrimeric G proteins. The ac cepted model for activation of heterotrimeric G proteins states that the pr otein dissociates to the free G(alpha)(GTP)-bound subunit and free G(beta g amma) dimer. On GTP hydrolysis, G(alpha) (CDP) then reassociates with G(bet a gamma)[Gilman, A. G. (1987) Annu. Rev. Biochem. 56, 615-649]. We reexamin ed this hypothesis, by using the mating G protein of the yeast Saccharomyce s cerevisiae encoded by the genes GPA1, STE4, and STE18 In the absence of m ating pheromone, the G(alpha) (Gpa1) subunit represses the mating pathway. On activation by binding of pheromone to a serpentine receptor, the G(beta gamma)(Ste4, Ste18) dimer transmits the signal to a mitogen-activated prote in kinase cascade, leading to gene activation, arrest in the G(1) stage of the cell cycle, production of shmoos (mating projections), and cell fusion. We found that a Ste4-Gpa1 fusion protein transmitted the pheromone signal and activated the mating pathway as effectively as when Ste4 (G(beta)) and Gpa1 (G(alpha)) were coexpressed as separate proteins. Hence, dissociation of this G protein is not required for its activation. Rather, a conformatio nal change in the heterotrimeric complex is likely to be involved in signal transduction.