Pharmacogenomic and structural analysis of constitutive G-protein coupled receptor activity
Smit, Martine J. (Vrije Universiteit Amsterdam)
Vischer, Henry F. (Vrije Universiteit Amsterdam)
Bakker, Remko A. (Vrije Universiteit Amsterdam)
Jongejan, Aldo (Vrije Universiteit Amsterdam)
Timmerman, Henk (Vrije Universiteit Amsterdam)
Pardo Carrasco, Leonardo (Universitat Autònoma de Barcelona. Departament de Pediatria, Obstetrícia i Ginecologia i Medicina Preventiva i Salut Pública)
Leurs, Rob (Vrije Universiteit Amsterdam)

Date:	2007
Abstract:	G-protein coupled receptors (GPCRs) respond to a chemically diverse plethora of signal transduction molecules. The notion that GPCRs also signal without an external chemical trigger, i. e. in a constitutive or spontaneous manner, resulted in a paradigm shift in the field of GPCR pharmacology. With the recognition of constitutive GPCR activity and the fact that GPCR binding and signaling can be strongly affected by a single point mutation, GPCR pharmacogenomics obtained a lot of attention. For a variety of GPCRs, point mutations have been convincingly linked to human disease. Mutations within conserved motifs, known to be involved in GPCR activation, might explain the properties of some naturally occurring constitutively active GPCR variants linked to disease. A brief history historical introduction to the present concept of constitutive receptor activity is given and the pharmacogenomic and the structural aspects of constitutive receptor activity are described.
Note:	Premi a l'excel·lència investigadora. Àmbit de les Ciències de la Salut. 2008
Rights:	Tots els drets reservats.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	PREI 2008 ; G-protein coupled receptors ; Constitutive activity ; Inverse agonism
Published in:	The Annual Review of Pharmacology and Toxicology, Vol. 47, Núm. (2007) , p. 53-87, ISSN 0362-1642

DOI: 10.1146/annurev.pharmtox.47.120505.105126

Post-print 42 p, 2.6 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles