Molecular mechanisms regulating Proteinase-Activated Receptors (PARs).
GPCR
PAR
agonist
antagonist
biased signaling
proteinases
regulatory motifs
structure-activity relationship
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
10
03
2021
received:
16
12
2020
accepted:
18
03
2021
pubmed:
21
3
2021
medline:
22
7
2021
entrez:
20
3
2021
Statut:
ppublish
Résumé
Proteinase-activated receptors (PARs) are a four-member family of G protein-coupled receptors defined by their irreversible proteolytic mechanism of activation. PARs have emerged as important regulators of various physiological responses and are implicated in numerous pathological conditions. Importantly, PAR1 and PAR4 are critical regulators of platelet function, while PAR2 is well established as a driver of inflammatory responses. PAR-targeted drug development efforts are therefore of great interest. In this review, we provide an overview of recent advances in our understanding of molecular mechanisms underlying PAR activation, effector interaction, and signaling. We also provide an overview of the diverse proteolytic enzymes that are now established as PAR regulators and describe the ability of different enzymes to elicit biased signaling through PARs. Finally, we highlight recent advances in the development of PAR-targeted pharmacological agents and discuss recent structure-activity relationship studies.
Substances chimiques
Antineoplastic Agents
0
F2RL1 protein, human
0
Receptor, PAR-1
0
Receptor, PAR-2
0
Receptors, G-Protein-Coupled
0
Receptors, Proteinase-Activated
0
Receptors, Thrombin
0
Peptide Hydrolases
EC 3.4.-
protease-activated receptor 4
JWE1M73YZN
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2697-2726Subventions
Organisme : CIHR
ID : 376560
Pays : Canada
Organisme : CIHR
ID : 376560
Pays : Canada
Informations de copyright
© 2021 Federation of European Biochemical Societies.
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