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Mol Biol Cell

Title:		Structurally unique interaction of RBD-like and PH domains is crucial for yeast pheromone signaling
Author(s):		Yerko V; Sulea T; Ekiel I; Harcus D; Baardsnes J; Cygler M; Whiteway M; Wu C;
Address:		"Life Sciences, National Research Council, Montreal, QC, Canada"
Journal Title:		Mol Biol Cell
Year:		2013
Volume:		20121214
Issue:		3
Page Number:		409 - 420
DOI:		10.1091/mbc.E12-07-0516
ISSN/ISBN:		1939-4586 (Electronic) 1059-1524 (Print) 1059-1524 (Linking)
Abstract:		"The Ste5 protein forms a scaffold that associates and regulates the components of the mitogen-activated protein (MAP) kinase cascade that controls mating-pheromone-mediated signaling in the yeast Saccharomyces cerevisiae. Although it is known that the MEK kinase of the pathway, Ste11, associates with Ste5, details of this interaction have not been established. We identified a Ras-binding-domain-like (RBL) region in the Ste11 protein that is required specifically for the kinase to function in the mating pathway. This module is structurally related to domains in other proteins that mediate Ras-MAP kinase kinase kinase associations; however, this RBL module does not interact with Ras, but instead binds the PH domain of the Ste5 scaffold. Structural and functional studies suggest that the key role of this PH domain is to mediate the Ste5-Ste11 interaction. Overall these two evolutionarily conserved modules interact with each other through a unique interface, and thus in the pheromone pathway the structural context of the RBL domain contribution to kinase activation has been shifted through a change of its interaction partner from Ras to a PH domain"
Keywords:		"Adaptor Proteins, Signal Transducing/*chemistry/genetics/metabolism Amino Acid Substitution Binding Sites Genes, Mating Type, Fungal MAP Kinase Kinase Kinases/*chemistry/genetics/metabolism Models, Molecular Mutagenesis, Site-Directed Peptide Mapping Pher;"
Notes:		"MedlineYerko, Volodymyr Sulea, Traian Ekiel, Irena Harcus, Doreen Baardsnes, Jason Cygler, Miroslaw Whiteway, Malcolm Wu, Cunle eng 42516-4/CAPMC/CIHR/Canada GSP-48370/CAPMC/CIHR/Canada Research Support, Non-U.S. Gov't 2012/12/18 Mol Biol Cell. 2013 Feb; 24(3):409-20. doi: 10.1091/mbc.E12-07-0516. Epub 2012 Dec 14"