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Integrating the GPCR transactivation-dependent and biased signalling paradigms in the context of PAR1 signalling
Little P.J.1; Hollenberg M.D.2; Kamato D.8; Thomas W.1; Chen J.7; Wang T.7; Zheng W.5; Osman N.8
2016
Source PublicationBritish Journal of Pharmacology
ISSN14765381 00071188
Volume173Issue:20Pages:2992-3000
Abstract

Classically, receptor-mediated signalling was conceived as a linear process involving one agonist, a variety of potential targets within a receptor family (e.g. α- and β-adrenoceptors) and a second messenger (e.g. cAMP)-triggered response. If distinct responses were stimulated by the same receptor in different tissues (e.g. lipolysis in adipocytes vs. increased beating rate in the heart caused by adrenaline), the differences were attributed to different second messenger targets in the different tissues. It is now realized that an individual receptor can couple to multiple effectors (different G proteins and different β-arrestins), even in the same cell, to drive very distinct responses. Furthermore, tailored agonists can mould the receptor conformation to activate one signal pathway versus another by a process termed ‘biased signalling’. Complicating issues further, we now know that activating one receptor can rapidly trigger the local release of agonists for a second receptor via a process termed ‘transactivation’. Thus, the end response can represent a cooperative signalling process involving two or more receptors linked by transactivation. This overview, with a focus on the GPCR, protease-activated receptor-1, integrates both of these processes to predict the complex array of responses that can arise when biased receptor signalling also involves the receptor transactivation process. The therapeutic implications of this signalling matrix are also briefly discussed. Linked Articles This article is part of a themed section on Molecular Pharmacology of G Protein-Coupled Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc.

DOI10.1111/bph.13398
URLView the original
Indexed BySCI
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000384823200005
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Cited Times [WOS]:5   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.University of Queensland
2.University of Calgary
3.Zhongshan Ophthalmic Center
4.Sun Yat-Sen University, Zhongshan School of Medicine
5.Universidade de Macau
6.Monash University
7.Sun Yat-Sen University
8.RMIT University
Recommended Citation
GB/T 7714
Little P.J.,Hollenberg M.D.,Kamato D.,et al. Integrating the GPCR transactivation-dependent and biased signalling paradigms in the context of PAR1 signalling[J]. British Journal of Pharmacology,2016,173(20):2992-3000.
APA Little P.J..,Hollenberg M.D..,Kamato D..,Thomas W..,Chen J..,...&Osman N..(2016).Integrating the GPCR transactivation-dependent and biased signalling paradigms in the context of PAR1 signalling.British Journal of Pharmacology,173(20),2992-3000.
MLA Little P.J.,et al."Integrating the GPCR transactivation-dependent and biased signalling paradigms in the context of PAR1 signalling".British Journal of Pharmacology 173.20(2016):2992-3000.
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