title: The Ste5 scaffold allosterically modulates signaling output of the yeast mating pathway.
abstract: Scaffold proteins organize signaling proteins into pathways and are often viewed as passive assembly platforms. We found that the Ste5 scaffold has a more active role in the yeast mating pathway: A fragment of Ste5 allosterically activated autophosphorylation of the mitogen-activated protein kinase Fus3. The resulting form of Fus3 is partially active-it is phosphorylated on only one of two key residues in the activation loop. Unexpectedly, at a systems level, autoactivated Fus3 appears to have a negative regulatory role, promoting Ste5 phosphorylation and a decrease in pathway transcriptional output. Thus, scaffolds not only direct basic pathway connectivity but can precisely tune quantitative pathway input-output properties.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California-San Francisco, 600 16th Street, San Francisco, CA 94143-2240, USA.
authors.forename: Roby P
authors.initials: RP
authors.lastname: Bhattacharyya
authors.forename: Attila
authors.initials: A
authors.lastname: Reményi
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Good
authors.forename: Caleb J
authors.initials: CJ
authors.lastname: Bashor
authors.forename: Arnold M
authors.initials: AM
authors.lastname: Falick
authors.forename: Wendell A
authors.initials: WA
authors.lastname: Lim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000494:Allosteric Regulation; D020816:Amino Acid Motifs; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015536:Down-Regulation; D004789:Enzyme Activation; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D009154:Mutation; D010675:Pheromones / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D010675:Pheromones; C080321:STE5 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C075580:FUS3 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases