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
Science
Date: Feb. 14, 2003
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