Pharmaceuticals 2011, 4(3), 509-523; doi:10.3390/ph4030509

Functional Consequences of GPCR Heterodimerization: GPCRs as Allosteric Modulators

1 Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 985850 Nebraska Medical Center, Omaha, NE 68198, USA 2 Department of Pediatrics, Emory University School of Medicine, and Children’s Healthcare of Atlanta Center for Cystic Fibrosis Research, 2015 Uppergate Drive, Atlanta, GA 30322, USA
* Author to whom correspondence should be addressed.
Received: 3 February 2011; in revised form: 9 March 2011 / Accepted: 9 March 2011 / Published: 14 March 2011
(This article belongs to the Special Issue GPCR Based Drug Discovery)
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Abstract: G Protein Coupled Receptors (GPCRs) represent the largest family of membrane proteins in the human genome, are the targets of approximately 25% of all marketed pharmaceuticals, and the focus of intensive research worldwide given that this superfamily of receptors is as varied in function as it is ubiquitously expressed among all cell types. Increasing evidence has shown that the classical two part model of GPCR signaling (one GPCR, one type of heterotrimeric G protein) is grossly oversimplified as many GPCRs can couple to more than one type of G protein, each subunit of the heterotrimeric G protein can activate different downstream effectors, and, surprisingly, other GPCRs can affect receptor behavior in G protein-independent ways. The concept of GPCR heterodimerization, or the physical association of two different types of GPCRs, presents an unexpected mechanism for GPCR regulation and function, and provides a novel target for pharmaceuticals. Here we present a synopsis of the functional consequences of GPCR heterodimerization in both in vitro and in vivo studies, focusing on the concept of GPCRs as allosteric modulators. Typically, an allosteric modulator is a ligand or molecule that alters a receptor’s innate functional properties, but here we propose that in the case of GPCR heterodimers, it is the physical coupling of two receptors that leads to changes in cognate receptor signaling.
Keywords: GPCR; heterodimer; allosteric modulator

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MDPI and ACS Style

Haack, K.K.; McCarty, N.A. Functional Consequences of GPCR Heterodimerization: GPCRs as Allosteric Modulators. Pharmaceuticals 2011, 4, 509-523.

AMA Style

Haack KK, McCarty NA. Functional Consequences of GPCR Heterodimerization: GPCRs as Allosteric Modulators. Pharmaceuticals. 2011; 4(3):509-523.

Chicago/Turabian Style

Haack, Karla K.V.; McCarty, Nael A. 2011. "Functional Consequences of GPCR Heterodimerization: GPCRs as Allosteric Modulators." Pharmaceuticals 4, no. 3: 509-523.

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