title: Variable Dependence of Signaling Output on Agonist Occupancy of Ste2p, a G Protein-coupled Receptor in Yeast.
abstract: We report here on the relationship between ligand binding and signaling responses in the yeast pheromone response pathway, a well characterized G protein-coupled receptor system. Responses to agonist (α-factor) by cells expressing widely varying numbers of receptors depend primarily on fractional occupancy, not the absolute number of agonist-bound receptors. Furthermore, the concentration of competitive antagonist required to inhibit α-factor-dependent signaling is more than 10-fold higher than predicted based on the known ligand affinities. Thus, responses to a particular number of agonist-bound receptors can vary greatly, depending on whether there are unoccupied or antagonist-bound receptors present on the same cell surface. This behavior does not appear to be due to pre-coupling of receptors to G protein or to the Sst2p regulator of G protein signaling. The results are consistent with a signaling response that is determined by the integration of positive signals from agonist-occupied receptors and inhibitory signals from unoccupied receptors, where the inhibitory signals can be diminished by antagonist binding.
authors.affiliation: From the Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642.
authors.forename: Rajashri
authors.initials: R
authors.lastname: Sridharan
authors.affiliation: From the Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Connelly
authors.affiliation: the Department of Chemistry and Macromolecular Assembly Institute, College of Staten Island of the City University of New York, Staten Island, New York 10314, and.|the Ph.D. Programs in Biochemistry and Chemistry, Graduate Center of the City University of New York, New York, New York 10016.
authors.forename: Fred
authors.initials: F
authors.lastname: Naider
authors.affiliation: From the Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, mark_dumont@urmc.rochester.edu.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Dumont
mesh_terms: D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D051964:Receptors, Mating Factor / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D020710:RGS Proteins
chemical_list: D020690:GTPase-Activating Proteins; D051964:Receptors, Mating Factor; D029701:Saccharomyces cerevisiae Proteins; C094301:SST2 protein, S cerevisiae; D020710:RGS Proteins; C498031:STE2 protein, S cerevisiae
keywords: G protein; G protein-coupled receptor (GPCR); pheromone; receptor; regulator of G protein signaling (RGS); signal transduction; signaling; yeast