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(Circulation Research. 2007;100:1109.)
© 2007 American Heart Association, Inc.

Editorials

G Proteins

More Than Transducers of Receptor-Generated Signals?

Stefan Engelhardt, Francesca Rochais

From the Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Wuerzburg, Germany.

Correspondence to Stefan Engelhardt, MD PhD, Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Wuerzburg, Versbacher Strasse 9, 97078 Wuerzburg, Germany. E-mail stefan.engelhardt@virchow.uni-wuerzburg.de

See related article, pages 1191–1199

Key Words: nucleoside diphosphate kinases • G protein signaling • cAMP • ß-adrenergic receptor

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Signaling through the activation of G proteins represents the most widely used signaling pathway in mammalian biology.^1,2 Classically, a transmembrane receptor comprising seven transmembrane domains (G protein-coupled receptor, GPCR) is activated by an extracellular stimulus and transduces this information to heterotrimeric G proteins through a conformational change of the receptor protein. Throughout evolution, a large variety of GPCRs has evolved to detect a wide spectrum of signals ranging from photons and odorants to endogenous neurotransmitters and hormones such as the catecholamines. Consequently, the majority of currently used drugs act on GPCRs. On receptor-mediated activation of the G protein -subunit, the bound GDP is exchanged against GTP and both the GTP-bound -subunit as well as the ß-subunits may activate downstream targets (Figure). As a GTPase, the -subunit then rapidly initiates its own inactivation through GTP-hydrolysis. This GTPase cycle of G protein activation and deactivation is subject to regulation by the RGS family of proteins (regulators of G protein signaling) that activate the GTPase function and thereby negatively regulate signaling of GPCRs.^3,4

View larger version (13K):   G protein dependent signaling in the cardiovascular system. Classically G proteins are activated through agonist occupied G protein-coupled receptors (GPCRs). In the inactive state, the G protein -subunit is bound to GDP, with a rapid exchange against GTP on activation. Both the -subunit and the ß-subunits can then activate diverse downstream signaling cascades. In addition G protein dependent signaling can be regulated independent from GPCR-activation through activators of G protein signaling (AGS) and nucleoside diphosphate kinase . . . [Full Text of this Article]

Related Article:

Regulation of Cardiac cAMP Synthesis and Contractility by Nucleoside Diphosphate Kinase B/G Protein ß Dimer Complexes

Hans-Joerg Hippe, Mark Luedde, Susanne Lutz, Henrike Koehler, Thomas Eschenhagen, Norbert Frey, Hugo A. Katus, Thomas Wieland, and Feraydoon Niroomand
Circ. Res. 2007 100: 1191-1199. [Abstract] [Full Text] [PDF]