Mechanistic pathways and biological roles for receptor-independent activators of G-protein signaling.
Blumer, Joe B. a,c; Smrcka, Alan V. b; Lanier, Stephen M. a,c,*
[Article] Pharmacology & Therapeutics. 113(3):488-506, March 2007.

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Signal processing via heterotrimeric G-proteins in response to cell surface receptors is a central and much investigated aspect of how cells integrate cellular stimuli to produce coordinated biological responses. The system is a target of numerous therapeutic agents and plays an important role in adaptive processes of organs; aberrant processing of signals through these transducing systems is a component of various disease states. In addition to G-protein coupled receptor (GPCR)-mediated activation of G-protein signaling, nature has evolved creative ways to manipulate and utilize the G[alpha][beta][gamma] heterotrimer or G[alpha] and G[beta][gamma] subunits independent of the cell surface receptor stimuli. In such situations, the G-protein subunits (G[alpha] and G[beta][gamma]) may actually be complexed with alternative binding partners independent of the typical heterotrimeric G[alpha][beta][gamma]. Such regulatory accessory proteins include the family of regulator of G-protein signaling (RGS) proteins that accelerate the GTPase activity of G[alpha] and various entities that influence nucleotide binding properties and/or subunit interaction. The latter group of proteins includes receptor-independent activators of G-protein signaling (AGS) proteins that play surprising roles in signal processing. This review provides an overview of our current knowledge regarding AGS proteins. AGS proteins are indicative of a growing number of accessory proteins that influence signal propagation, facilitate cross talk between various types of signaling pathways, and provide a platform for diverse functions of both the heterotrimeric G[alpha][beta][gamma] and the individual G[alpha] and G[beta][gamma] subunits.

(C) 2007Elsevier, Inc.