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Science 311 (5762): 822-826

Copyright © 2006 by the American Association for the Advancement of Science

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

Roby P. Bhattacharyya,1,2* Attila Reményi,1* Matthew C. Good,1,2 Caleb J. Bashor,1,3 Arnold M. Falick,4 Wendell A. Lim1{dagger}

Abstract: 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.

1 Department of Cellular and Molecular Pharmacology, University of California–San Francisco, 600 16th Street, San Francisco, CA 94143–2240, USA.
2 Program in Biological Sciences, University of California–San Francisco, 600 16th Street, San Francisco, CA 94143–2240, USA.
3 Graduate Group in Biophysics, University of California–San Francisco, 600 16th Street, San Francisco, CA 94143–2240, USA.
4 Howard Hughes Medical Institute Mass Spectrometry Laboratory, University of California–Berkeley, 17 Barker Hall, Berkeley, CA 94720, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: lim{at}cmp.ucsf.edu


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