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Science. 2006 Feb 10;311(5762):822-6. Epub 2006 Jan 19.

The Ste5 scaffold allosterically modulates signaling output of the yeast mating pathway.

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  • 1Department of Cellular and Molecular Pharmacology, University of California-San Francisco, 600 16th Street, San Francisco, CA 94143-2240, USA.

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.

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PMID:
16424299
[PubMed - indexed for MEDLINE]
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