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Mol Cell

Title:		A membrane binding domain in the ste5 scaffold synergizes with gbetagamma binding to control localization and signaling in pheromone response
Author(s):		Winters MJ; Lamson RE; Nakanishi H; Neiman AM; Pryciak PM;
Address:		"Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01605, USA"
Journal Title:		Mol Cell
Year:		2005
Volume:		20
Issue:		1
Page Number:		21 - 32
DOI:		10.1016/j.molcel.2005.08.020
ISSN/ISBN:		1097-2765 (Print) 1097-2765 (Linking)
Abstract:		"Activation of mitogen-activated protein (MAP) kinase cascade signaling by yeast mating pheromones involves recruitment of the Ste5 scaffold protein to the plasma membrane by the receptor-activated Gbetagamma dimer. Here, we identify a putative amphipathic alpha-helical domain in Ste5 that binds directly to phospholipid membranes and is required for membrane recruitment by Gbetagamma. Thus, Ste5 signaling requires synergistic Ste5-Gbetagamma and Ste5-membrane interactions, with neither alone being sufficient. Remarkably, the Ste5 membrane binding domain is a dual-function motif that also mediates nuclear import. Separation-of-function mutations show that signaling requires the membrane-targeting activity of this domain, not its nuclear-targeting activity, and heterologous lipid binding domains can substitute for its function. This domain also contains imperfections that reduce membrane affinity, and their elimination results in constitutive signaling, explaining some previous hyperactive Ste5 mutants. Therefore, weak membrane affinity is advantageous, ensuring a normal level of signaling quiescence in the absence of stimulus and imposing a requirement for Gbetagamma binding"
Keywords:		"Active Transport, Cell Nucleus/physiology Adaptor Proteins, Signal Transducing/genetics/*metabolism Cell Membrane/genetics/*metabolism Heterotrimeric GTP-Binding Proteins/genetics/*metabolism MAP Kinase Signaling System/*physiology Pheromones/genetics/*me;"
Notes:		"MedlineWinters, Matthew J Lamson, Rachel E Nakanishi, Hideki Neiman, Aaron M Pryciak, Peter M eng R01 GM057769/GM/NIGMS NIH HHS/ GM57769/GM/NIGMS NIH HHS/ R01 GM057769-06/GM/NIGMS NIH HHS/ GM62184/GM/NIGMS NIH HHS/ R01 GM057769-07/GM/NIGMS NIH HHS/ R01 GM057769-08/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S. 2005/10/08 Mol Cell. 2005 Oct 7; 20(1):21-32. doi: 10.1016/j.molcel.2005.08.020"