Regulation of Cell Function by RGS Proteins

Washington University School Of Medicine, Saint Louis MO

Investigators

Abstract

As transducers of sensory stimuli and extracellular signals, G protein coupled receptors and the signaling pathways they activate are important regulators of cell function throughout development and adult life. They regulate cell differentiation, proliferation, motility and membrane excitability, which have key roles in living systems. A fundamental challenge is to determine how cells elaborate specific and temporally regulated responses when challenged with stimuli that trigger G protein signaling pathways. New insights into the mechanisms governing the specificity and temporal regulation of G protein signaling pathways have been provided by the recent discovery of RGS proteins (regulators of G protein signaling), a novel family of more than 20 regulatory proteins. RGS proteins can limit the strength or duration of cellular responses by acting as GAPs (GTPase activating proteins) that stimulate the ability of G protein alpha subunits to hydrolyze GTP. Certain RGS family members can act as effectors, mediating specific responses triggered by agonist stimulation. Because RGS proteins probably have additional functions, further studies of these proteins should yield novel insights into the mechanisms whereby G proteins control cell function. The long term objective of this project is to delineate the mechanisms whereby cell function is regulated by RGS proteins. Currently the focus of this project is on RGS2, which is expressed in various organs and tissues where it potentially regulates a number of G protein dependent signaling pathways. This project will determine if the selectivity of RGS2 toward Gq is an important determinant of biological function. These studies will aid in our understanding of how signals are transmitted and regulated in cells.