The yeast pheromone-responsive Ga protein stimulates recovery from chronic pheromone treatment by two mechanisms that are activated at distinct levels of stimulus

• Published in: Cell biochemistry and biophysics Vol. 30; no. 2; pp. 193 - 212
• Main Authors: Zhou, Jianlong, Arora, Michelle, Stone, David E
• Format: Journal Article
• Language: English
• Published: 01.06.1999
• Subjects: Adaptations; Cell cycle; Epistasis; Guanine nucleotide-binding protein; Guanosine; Guanosinetriphosphatase; MAP kinase; Mating; Pheromone receptors; Pheromones; Triphosphatase
• ISSN: 1085-9195; 1559-0283
• DOI: 10.1007/BF02738067

The pheromone response ofSaccharomyces cerevisiae is mediated by a receptor-coupled heterotrimeric G protein. The bg subunit of the G protein stimulates a PAK/MAP kinase cascade that leads to cellular changes preparatory to mating, while the pheromone-responsive Ga protein, Gpa1, antagonizes the Gbg-induced signal. In its inactive conformation, Gpa1 sequesters Gbg and tethers it to the receptor. In its active conformation, Gpa1 stimulates adaptive mechanisms that downregulate the mating signal, but which are independent of a-bg binding. To elucidate these potentially novel signaling functions of Ga in yeast, epistasis analyses were performed using N388D, a hyperadaptive mutant form of Gpa1, and null alleles of various loci that have been implicated in adaptation. The results of these experiments indicate the existence of signaling thresholds that affect the yeast mating reaction. At low pheromone concentration, the Regulator of G Protein Signaling (RGS) homologue and putative guanosine triphosphatase (GTPase) activating protein, Sst2, appears to stimulate sequestration of Gbg by Gpa1. Throughout the range of pheromone concentrations sufficient to cause cell cycle arrest, Gpa1 stimulates adaptive mechanisms that are partially dependent on Msg5 and Mpt5. Gpa1-mediated adaptation appears to be independent of Afr1, Akr1, and the carboxy-terminus of the pheromone receptor.