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Science

Title:		Conformational control of the Ste5 scaffold protein insulates against MAP kinase misactivation
Author(s):		Zalatan JG; Coyle SM; Rajan S; Sidhu SS; Lim WA;
Address:		"Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158, USA"
Journal Title:		Science
Year:		2012
Volume:		20120809
Issue:		6099
Page Number:		1218 - 1222
DOI:		10.1126/science.1220683
ISSN/ISBN:		1095-9203 (Electronic) 0036-8075 (Print) 0036-8075 (Linking)
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"
Keywords:		"Adaptor Proteins, Signal Transducing/antagonists & inhibitors/*chemistry/*metabolism Enzyme Activation MAP Kinase Kinase Kinases/metabolism MAP Kinase Signaling System Mitogen-Activated Protein Kinase Kinases/metabolism Mitogen-Activated Protein Kinases/*;"
Notes:		"MedlineZalatan, Jesse G Coyle, Scott M Rajan, Saravanan Sidhu, Sachdev S Lim, Wendell A eng R01 GM62583/GM/NIGMS NIH HHS/ MOPS-93725/CAPMC/CIHR/Canada P50 GM081879/GM/NIGMS NIH HHS/ R01 GM062583/GM/NIGMS NIH HHS/ R01 GM055040/GM/NIGMS NIH HHS/ PN2 EY016546/EY/NEI NIH HHS/ P41 RR001614/RR/NCRR NIH HHS/ HHMI/Howard Hughes Medical Institute/ R01 GM55040/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 2012/08/11 Science. 2012 Sep 7; 337(6099):1218-22. doi: 10.1126/science.1220683. Epub 2012 Aug 9"