The yeast pheromone-responsive G alpha protein stimulates recovery from chronic pheromone treatment by two mechanisms that are activated at distinct levels of stimulus.
The pheromone response of Saccharomyces cerevisiae is mediated by a receptor-coupled heterotrimeric G protein. The beta gamma subunit of the G protein stimulates a PAK/MAP kinase cascade that leads to cellular changes preparatory to mating, while the pheromone-responsive G alpha protein, Gpa1, antagonizes the G beta gamma-induced signal. In its inactive conformation, Gpa1 sequesters G beta gamma and tethers it to the receptor. In its active conformation, Gpa1 stimulates adaptive mechanisms that downregulate the mating signal, but which are independent of alpha-beta gamma binding. To elucidate these potentially novel signaling functions of G alpha 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 G beta gamma 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.
Zhou
J
J
Laboratory for Molecular Biology, University of Illinois at Chicago 60607, USA. U62248@uicvm.uic.edu
Arora
M
M
Stone
D E
DE
D000217:Acyltransferases; D015536:Down-Regulation; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000502:physiology; D044385:GTP-Binding Protein alpha Subunits; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D019204:GTP-Binding Proteins / Q000502:physiology*; D020690:GTPase-Activating Proteins; D017930:Genes, Reporter; D020962:Heterotrimeric GTP-Binding Proteins; D008954:Models, Biological; D010675:Pheromones / Q000009:adverse effects* / Q000502:physiology*; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D014157:Transcription Factors; D020710:RGS Proteins
D000217:Acyltransferases; D005656:Fungal Proteins; D044385:GTP-Binding Protein alpha Subunits; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D019204:GTP-Binding Proteins; D020690:GTPase-Activating Proteins; D020962:Heterotrimeric GTP-Binding Proteins; D010675:Pheromones; D017027:Protein Tyrosine Phosphatases; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C083723:AFR1 protein, S cerevisiae; C118981:G-protein Beta gamma; C094301:SST2 protein, S cerevisiae; D020710:RGS Proteins; C107846:AKR1 protein, S cerevisiae; C085791:MSG5 protein, S cerevisiae; C084293:GPA1 protein, S cerevisiae