Lim Lab | Papers

Rewiring MAP Kinase Pathways Using Alternative Scaffold Assembly Mechanisms

Sang-Hyun Park, Ali Zarrinpar, and Wendell A. Lim
Science 299, 1061-1064 (2003)

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 find that the yeast mitogen-activated protein (MAP) kinase scaffold Ste5 is tolerant to major stereochemical perturbations; heterologous protein interactions can 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 can 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.

Supplemental Data
Commentary in Science by Mark Ptashne and Alexander Gann
Commentary in Molecular Cell by James E. Ferrell, Jr. and Karlene A. Cimprich