IUPHAR/BPS Guide to Pharmacology CITE
https://doi.org/10.2218/gtopdb/F59/2023.1

Proteinase-activated receptors in GtoPdb v.2023.1



Nigel Bunnett1, Kathryn DeFea2, Justin Hamilton1, Morley D. Hollenberg3, Rithwik Ramachandran4 and JoAnn Trejo5
  1. Monash University, Australia
  2. University of California Riverside, USA
  3. University of Calgary, Canada
  4. University of Western Ontario, Canada
  5. University of California San Diego, USA


Abstract

Proteinase-activated receptors (PARs, nomenclature as agreed by the NC-IUPHAR Subcommittee on Proteinase-activated Receptors [39]) are unique members of the GPCR superfamily activated by proteolytic cleavage of their amino terminal exodomains. Agonist proteinase-induced hydrolysis unmasks a tethered ligand (TL) at the exposed amino terminus, which acts intramolecularly at the binding site in the body of the receptor to effect transmembrane signalling. TL sequences at human PAR1-4 are SFLLRN-NH2, SLIGKV-NH2, TFRGAP-NH2 and GYPGQV-NH2, respectively. With the exception of PAR3, synthetic peptides with these sequences (as carboxyl terminal amides) are able to act as agonists at their respective receptors. Several proteinases, including neutrophil elastase, cathepsin G and chymotrypsin can have inhibitory effects at PAR1 and PAR2 such that they cleave the exodomain of the receptor without inducing activation of Gαq-coupled calcium signalling, thereby preventing activation by activating proteinases but not by agonist peptides. Neutrophil elastase (NE) cleavage of PAR1 and PAR2 can however activate MAP kinase signaling by exposing a TL that is different from the one revealed by trypsin [87]. PAR2 activation by NE regulates inflammation and pain responses [115, 76] and triggers mucin secretion from airway epithelial cells [116].

Contents

This is a citation summary for Proteinase-activated receptors in the Guide to Pharmacology database (GtoPdb). It exists purely as an adjunct to the database to facilitate the recognition of citations to and from the database by citation analyzers. Readers will almost certainly want to visit the relevant sections of the database which are given here under database links.

GtoPdb is an expert-driven guide to pharmacological targets and the substances that act on them. GtoPdb is a reference work which is most usefully represented as an on-line database. As in any publication this work should be appropriately cited, and the papers it cites should also be recognized. This document provides a citation for the relevant parts of the database, and also provides a reference list for the research cited by those parts. For further details see [18].

Please note that the database version for the citations given in GtoPdb are to the most recent preceding version in which the family or its subfamilies and targets were substantially changed. The links below are to the current version. If you need to consult the cited version, rather than the most recent version, please contact the GtoPdb curators.

Database links

Proteinase-activated receptors
https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=59
Introduction to Proteinase-activated receptors
https://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=59
    Receptors
            PAR1
            https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=347
            PAR2
            https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=348
            PAR3
            https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=349
            PAR4
            https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=350

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