The Ste5 scaffold allosterically modulates signaling output of the yeast mating pathway.
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.
Pubmed ID: 16424299 RIS Download
Adaptor Proteins, Signal Transducing | Allosteric Regulation | Amino Acid Motifs | Binding Sites | Crystallography, X-Ray | Down-Regulation | Enzyme Activation | MAP Kinase Signaling System | Mitogen-Activated Protein Kinases | Models, Biological | Models, Molecular | Mutation | Pheromones | Phosphorylation | Protein Binding | Protein Conformation | Protein Structure, Secondary | Protein Structure, Tertiary | Saccharomyces cerevisiae | Saccharomyces cerevisiae Proteins | Transcription, Genetic