PerspectiveProtein Interactions

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

Science Signaling  23 Jan 2007:
Vol. 2007, Issue 370, pp. pe2
DOI: 10.1126/stke.3702007pe2

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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 Gα-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.

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