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

Authors:
Bhattacharyya RP, Reményi A, Good MC, Bashor CJ, Falick AM, Lim WA
Affiliation:
Journal:
Science (New York, N.Y.)

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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