Conformational control of the Ste5 scaffold protein insulates against MAP kinase misactivation.

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158, USA.
Science (Impact Factor: 31.48). 08/2012; 337(6099):1218-22. DOI: 10.1126/science.1220683
Source: PubMed

ABSTRACT Cells reuse signaling proteins in multiple pathways, raising the potential for improper cross talk. Scaffold proteins are thought to insulate against such miscommunication by sequestering proteins into distinct physical complexes. We show that the scaffold protein Ste5, which organizes the yeast mating mitogen-activated protein kinase (MAPK) pathway, does not use sequestration to prevent misactivation of the mating response. Instead, Ste5 appears to use a conformation mechanism: Under basal conditions, an intramolecular interaction of the pleckstrin homology (PH) domain with the von Willebrand type A (VWA) domain blocks the ability to coactivate the mating-specific MAPK Fus3. Pheromone-induced membrane binding of Ste5 triggers release of this autoinhibition. Thus, in addition to serving as a conduit guiding kinase communication, Ste5 directly receives input information to decide if and when signal can be transmitted to mating output.


Available from: Scott Coyle, Dec 16, 2013
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