Rewiring MAP kinase pathways using alternative scaffold assembly mechanisms.
How scaffold proteins control information flow in signaling pathways is poorly understood: Do they simply tether components, or do they precisely orient and activate them? We found that the yeast mitogen-activated protein (MAP) kinase scaffold Ste5 is tolerant to major stereochemical perturbations; heterologous protein interactions could functionally replace native kinase ... recruitment interactions, indicating that simple tethering is largely sufficient for scaffold-mediated signaling. Moreover, by engineering a scaffold that tethers a unique kinase set, we could create a synthetic MAP kinase pathway with non-natural input-output properties. These findings demonstrate that scaffolds are highly flexible organizing factors that can facilitate pathway evolution and engineering.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Binding Sites, Carrier Proteins, Evolution, Molecular, MAP Kinase Kinase Kinases, MAP Kinase Signaling System, Membrane Proteins, Mitogen-Activated Protein Kinase Kinases, Mitogen-Activated Protein Kinases, Mutation, Osmolar Concentration, Phosphorylation, Protein Binding, Protein Conformation, Protein Kinases, Protein Precursors, Protein Structure, Tertiary, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Substrate Specificity
Adaptor Proteins, Signal Transducing, Binding Sites, Carrier Proteins, Evolution, Molecular, MAP Kinase Kinase Kinases, MAP Kinase Signaling System, Membrane Proteins, Mitogen-Activated Protein Kinase Kinases, Mitogen-Activated Protein Kinases, Mutation, Osmolar Concentration, Phosphorylation, Protein Binding, Protein Conformation, Protein Kinases, Protein Precursors, Protein Structure, Tertiary, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Substrate Specificity
Science
Date: Feb. 14, 2003
PubMed ID: 12511654
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