Lim Lab | Papers

The Ste5 Scaffold Allosterically Modulates Signaling Output of the Yeast Mating Pathway

Roby P. Bhattacharyya*, Attila Reményi*, Matthew C. Good, Caleb J. Bashor, Arnold M. Falick, and Wendell A. Lim
Science 311, 822-826 (2006)

Scaffold proteins organize signaling proteins into pathways and are often viewed as passive assembly platforms. We found that the Ste5 scaffold has a more active role in the yeast mating pathway: A fragment of Ste5 allosterically activated autophosphorylation of the mitogen-activated protein kinase Fus3. The resulting form of Fus3 is partially active-it is phosphorylated on only one of two key residues in the activation loop. Unexpectedly, at a systems level, autoactivated Fus3 appears to have a negative regulatory role, promoting Ste5 phosphorylation and a decrease in pathway transcriptional output. Thus, scaffolds not only direct basic pathway connectivity but can precisely tune quantitative pathway input-output properties.

Commentary in Science by Ashton Breitkreutz and Mike Tyers