| Title: | "Variable Dependence of Signaling Output on Agonist Occupancy of Ste2p, a G Protein-coupled Receptor in Yeast" |
| Author(s): | Sridharan R; Connelly SM; Naider F; Dumont ME; |
| Address: | "From the Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642. 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. From the Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, mark_dumont@urmc.rochester.edu" |
| ISSN/ISBN: | 1083-351X (Electronic) 0021-9258 (Print) 0021-9258 (Linking) |
| 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 (alpha-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 alpha-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" |
| Keywords: | "GTPase-Activating Proteins/genetics/*metabolism Receptors, Mating Factor/genetics/*metabolism Saccharomyces cerevisiae/genetics/*metabolism Saccharomyces cerevisiae Proteins/genetics/*metabolism Signal Transduction/*physiology G protein G protein-coupled;" |
| Notes: | "MedlineSridharan, Rajashri Connelly, Sara M Naider, Fred Dumont, Mark E eng R01 GM022087/GM/NIGMS NIH HHS/ R01 GM059357/GM/NIGMS NIH HHS/ R01 GM084083/GM/NIGMS NIH HHS/ R01 GM114974/GM/NIGMS NIH HHS/ 2016/09/21 J Biol Chem. 2016 Nov 11; 291(46):24261-24279. doi: 10.1074/jbc.M116.733006. Epub 2016 Sep 19" |
