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Bhattacharyya, RP, Reményi, A, Good, MC, Bashor, CJ, Falick, AM and Lim, WA (2006) The Ste5 scaffold allosterically modulates signaling output of the yeast mating pathway. Science 311:822-6
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.
Adaptor Proteins, Signal Transducing/chemistry; Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Allosteric Regulation; Amino Acid Motifs; Binding Sites; Crystallography, X-Ray; Down-Regulation; Enzyme Activation; MAP Kinase Signaling System; Mitogen-Activated Protein Kinases/chemistry; Mitogen-Activated Protein Kinases/metabolism; Models, Biological; Models, Molecular; Mutation; Pheromones/physiology; Phosphorylation; Protein Binding; Protein Conformation; Protein Structure, Secondary; Protein Structure, Tertiary; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/chemistry; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Transcription, Genetic
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