Rewiring MAP Kinase Pathways Using Alternative Scaffold Assembly Mechanisms
Abstract
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.
- Publication:
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Science
- Pub Date:
- February 2003
- DOI:
- 10.1126/science.1076979
- Bibcode:
- 2003Sci...299.1061P
- Keywords:
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- CELL BIOL