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Mol Cell Biol

Title:		Localization and signaling of G(beta) subunit Ste4p are controlled by a-factor receptor and the a-specific protein Asg7p
Author(s):		Kim J; Bortz E; Zhong H; Leeuw T; Leberer E; Vershon AK; Hirsch JP;
Address:		"Department of Cell Biology and Anatomy, Mount Sinai School of Medicine, New York, New York 10029, USA"
Journal Title:		Mol Cell Biol
Year:		2000
Volume:		20
Issue:		23
Page Number:		8826 - 8835
DOI:		10.1128/MCB.20.23.8826-8835.2000
ISSN/ISBN:		0270-7306 (Print) 1098-5549 (Electronic) 0270-7306 (Linking)
Abstract:		"Haploid yeast cells initiate pheromone signaling upon the binding of pheromone to its receptor and activation of the coupled G protein. A regulatory process termed receptor inhibition blocks pheromone signaling when the a-factor receptor is inappropriately expressed in MATa cells. Receptor inhibition blocks signaling by inhibiting the activity of the G protein beta subunit, Ste4p. To investigate how Ste4p activity is inhibited, its subcellular location was examined. In wild-type cells, alpha-factor treatment resulted in localization of Ste4p to the plasma membrane of mating projections. In cells expressing the a-factor receptor, alpha-factor treatment resulted in localization of Ste4p away from the plasma membrane to an internal compartment. An altered version of Ste4p that is largely insensitive to receptor inhibition retained its association with the membrane in cells expressing the a-factor receptor. The inhibitory function of the a-factor receptor required ASG7, an a-specific gene of previously unknown function. ASG7 RNA was induced by pheromone, consistent with increased inhibition as the pheromone response progresses. The a-factor receptor inhibited signaling in its liganded state, demonstrating that the receptor can block the signal that it initiates. ASG7 was required for the altered localization of Ste4p that occurs during receptor inhibition, and the subcellular location of Asg7p was consistent with its having a direct effect on Ste4p localization. These results demonstrate that Asg7p mediates a regulatory process that blocks signaling from a G protein beta subunit and causes its relocalization within the cell"
Keywords:		"Cell Compartmentation Fungal Proteins/metabolism *GTP-Binding Protein beta Subunits Gene Expression Regulation, Fungal Heterotrimeric GTP-Binding Proteins/*metabolism Models, Biological Pheromones/*metabolism Protein Binding Receptors, Cell Surface/*metab;"
Notes:		"MedlineKim, J Bortz, E Zhong, H Leeuw, T Leberer, E Vershon, A K Hirsch, J P eng R01 GM049265/GM/NIGMS NIH HHS/ GM49265/GM/NIGMS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 2000/11/14 Mol Cell Biol. 2000 Dec; 20(23):8826-35. doi: 10.1128/MCB.20.23.8826-8835.2000"