Science · 2003 · 361 citations · 20 references
Life SciencesBiological EngineeringMolecular BiologyCell SignalingSignal TransductionSynthetic BiologyCell-scaffold InteractionsProtein Kinase CascadesProtein Scaffold EngineeringScaffold ConstructionScaffold DesignScaffold ProteinsInformation Flow ControlKinase Scaffold ProteinsProtein ScaffoldingScaffold Protein InteractionsScaffold Protein-mediated SignalingScaffold Proteins In Kinase CascadesScaffold Proteins In Signal TransductionScaffold Proteins In Signaling
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.
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A novel genetic system to detect protein–protein interactions
Stanley Fields, Ok-Kyu Song · Nature · 1989 · 6.1K citations
A multivalent PDZ-domain protein assembles signalling complexes in a G-protein-coupled cascade
Susan Tsunoda, Jimena Sierralta, Yumei Sun et al. · Nature · 1997 · 617 citations