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J Biol Chem

Title:		Regulators of G protein signaling and transient activation of signaling: experimental and computational analysis reveals negative and positive feedback controls on G protein activity
Author(s):		Hao N; Yildirim N; Wang Y; Elston TC; Dohlman HG;
Address:		"Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-0812, USA"
Journal Title:		J Biol Chem
Year:		2003
Volume:		20030910
Issue:		47
Page Number:		46506 - 46515
DOI:		10.1074/jbc.M308432200
ISSN/ISBN:		0021-9258 (Print) 0021-9258 (Linking)
Abstract:		"Cellular responses to hormones and neurotransmitters are necessarily transient. The mating pheromone signal in yeast is typical. Signal initiation requires cell surface receptors, a G protein heterotrimer, and down-stream effectors. Signal inactivation requires Sst2, a regulator of G protein signaling (RGS) protein that accelerates GTPase activity. We conducted a quantitative analysis of RGS and G protein expression and devised computational models that describe their activity in vivo. These results indicated that pheromone-dependent transcriptional induction of the RGS protein constitutes a negative feedback loop that leads to desensitization. Modeling also suggested the presence of a positive feedback loop leading to resensitization of the pathway. In confirmation of the model, we found that the RGS protein is ubiquitinated and degraded in response to pheromone stimulation. We identified and quantitated these positive and negative feedback loops, which account for the transient response to external signals observed in vivo"
Keywords:		"Computer Simulation Feedback, Physiological GTPase-Activating Proteins Gene Expression Regulation Heterotrimeric GTP-Binding Proteins/*physiology Pheromones Saccharomyces cerevisiae Proteins/physiology *Signal Transduction Time Factors Transcription, Gene;"
Notes:		"MedlineHao, Nan Yildirim, Necmettin Wang, Yuqi Elston, Timothy C Dohlman, Henrik G eng R01 GM055316/GM/NIGMS NIH HHS/ R01 GM059167/GM/NIGMS NIH HHS/ GM 55316/GM/NIGMS NIH HHS/ GM 59167/GM/NIGMS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. 2003/09/12 J Biol Chem. 2003 Nov 21; 278(47):46506-15. doi: 10.1074/jbc.M308432200. Epub 2003 Sep 10"