Rewiring MAP kinase pathways using alternative scaffold assembly mechanisms |
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Authors: | Park Sang-Hyun Zarrinpar Ali Lim Wendell A |
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Institution: | Department of Cellular and Molecular Pharmacology and Department of Biochemistry and Biophysics, University of California, 513 Parnassus Avenue, San Francisco, CA 94143, USA. |
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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. |
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