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Science 299 (5609): 1061-1064

Copyright © 2003 by the American Association for the Advancement of Science

Rewiring MAP Kinase Pathways Using Alternative Scaffold Assembly Mechanisms

Sang-Hyun Park, Ali Zarrinpar, Wendell A. Lim*

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.

Department of Cellular and Molecular Pharmacology and Department of Biochemistry and Biophysics, University of California, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
*   To whom correspondence should be addressed. E-mail: wlim{at}itsa.ucsf.edu

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