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Genetics

Title:		Mapping of a yeast G protein betagamma signaling interaction
Author(s):		Dowell SJ; Bishop AL; Dyos SL; Brown AJ; Whiteway MS;
Address:		"Glaxo Wellcome Research and Development, Stevenage, SG1 2NY, United Kingdom. sd14041@glaxowellcome.co.uk"
Journal Title:		Genetics
Year:		1998
Volume:		150
Issue:		4
Page Number:		1407 - 1417
DOI:		10.1093/genetics/150.4.1407
ISSN/ISBN:		0016-6731 (Print) 0016-6731 (Linking)
Abstract:		"The mating pathway of Saccharomyces cerevisiae is widely used as a model system for G protein-coupled receptor-mediated signal transduction. Following receptor activation by the binding of mating pheromones, G protein betagamma subunits transmit the signal to a MAP kinase cascade, which involves interaction of Gbeta (Ste4p) with the MAP kinase scaffold protein Ste5p. Here, we identify residues in Ste4p required for the interaction with Ste5p. These residues define a new signaling interface close to the Ste20p binding site within the Gbetagamma coiled-coil. Ste4p mutants defective in the Ste5p interaction interact efficiently with Gpa1p (Galpha) and Ste18p (Ggamma) but cannot function in signal transduction because cells expressing these mutants are sterile. Ste4 L65S is temperature-sensitive for its interaction with Ste5p, and also for signaling. We have identified a Ste5p mutant (L196A) that displays a synthetic interaction defect with Ste4 L65S, providing strong evidence that Ste4p and Ste5p interact directly in vivo through an interface that involves hydrophobic residues. The correlation between disruption of the Ste4p-Ste5p interaction and sterility confirms the importance of this interaction in signal transduction. Identification of the Gbetagamma coiled-coil in Ste5p binding may set a precedent for Gbetagamma-effector interactions in more complex organisms"
Keywords:		"*Adaptor Proteins, Signal Transducing Amino Acid Sequence *Carrier Proteins Fungal Proteins/genetics/*metabolism *GTP-Binding Protein alpha Subunits GTP-Binding Protein alpha Subunits, Gq-G11 *GTP-Binding Protein beta Subunits *GTP-Binding Protein gamma S;"
Notes:		"MedlineDowell, S J Bishop, A L Dyos, S L Brown, A J Whiteway, M S eng 1998/12/02 Genetics. 1998 Dec; 150(4):1407-17. doi: 10.1093/genetics/150.4.1407"