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Sci. STKE, 23 January 2007
Vol. 2007, Issue 370, p. pe2
[DOI: 10.1126/stke.3702007pe2]

PERSPECTIVES

RGS Proteins: Swiss Army Knives in Seven-Transmembrane Domain Receptor Signaling Networks

Scott P. Heximer1* and Kendall J. Blumer2*

1Department of Physiology and Heart and Stroke/Richard Lewar Centre of Excellence, University of Toronto, 1 King’s College Circle, Toronto, Ontario M5S 1A8, Canada.
2Department of Cell Biology and Physiology, Washington University School of Medicine, Box 8228, 660 South Euclid Avenue, St. Louis, MO 63110, USA.

Abstract: Coordinated regulation of heterotrimeric guanine nucleotide–binding protein (G protein) activity is critical for the integration of information from multiple intracellular signaling networks. The human regulator of G protein signaling (RGS) protein family contains more than 35 members that are well suited for this purpose. Although all RGS proteins contain a core ~120–amino acid G{alpha}-interacting domain (called the RGS domain), they differ widely in size and organization of other functional domains. Architecturally complex RGS proteins contain multiple modular protein-protein interaction domains that mediate their interaction with diverse signaling effectors. Architecturally simple RGS proteins contain small amino-terminal domains; however, they show surprising versatility in the number of intracellular partners with which they interact. This Perspective focuses on RGS2, a simple RGS protein with the potential to integrate multiple signaling networks. In three recent studies, the amino-terminal domain of RGS2 was shown to interact with and regulate three different effector proteins: adenylyl cyclase, tubulin, and the cation channel TRPV6. To explain this growing list of RGS2-interacting partners, we propose two models: (i) The amino-terminal domain of RGS2 comprises several short effector protein interaction motifs; (ii) the amino-terminal domain of RGS2 adopts distinct structures to bind various targets. Whatever the precise mechanism controlling its target interactions, these studies suggest that RGS2 is a key point of integration for multiple intracellular signaling pathways, and they highlight the role of RGS proteins as dynamic, multifunctional signaling centers that coordinate a diverse range of cellular functions.

*Corresponding author. E-mail, scott.heximer{at}utoronto.ca (S.P.H.); kblumer{at}cellbiology.wustl.edu (K.J.B.)

Citation: S. P. Heximer, K. J. Blumer, RGS Proteins: Swiss Army Knives in Seven-Transmembrane Domain Receptor Signaling Networks. Sci. STKE 2007, pe2 (2007).

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