Mouse F2r

Figure. Concentration-dependent activation of F2r by

Reporter cells were transfected with either the expression plasmid for mouse coagulation factor ⅠⅠ (thrombin) receptor (F2r) or the mock plasmid and treated with various concentrations of the reference agonist. Data points shown are the mean ± SEM of an experiment (n = 4).

coagulation factor ⅠⅠ (thrombin) receptor
Available assay modes
Agonist, Inverse agonist, Antagonist, PAM, NAM
à la carte, Mouse non-orphan GPCRs

Proteinase-activated receptors

Proteinase-activated receptors (PARs) 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 [1]. PAR2 activation by NE regulates inflammation and pain responses [2,3] and triggers mucin secretion from airway epithelial cells [4].


  1. Ramachandran R, Noorbakhsh F, Defea K, et al. Targeting proteinase-activated receptors: therapeutic potential and challenges. Nat Rev Drug Discov 2012;11:69-86.
  2. Zhao P, Lieu T, Barlow N, et al. Neutrophil Elastase Activates Protease-activated Receptor-2 (PAR2) and Transient Receptor Potential Vanilloid 4 (TRPV4) to Cause Inflammation and Pain. J Biol Chem 2015;290:13875-87.
  3. Muley MM, Reid AR, Botz B, et al. Neutrophil elastase induces inflammation and pain in mouse knee joints via activation of proteinase-activated receptor-2. Br J Pharmacol 2016;173:766-77.
  4. Zhou J, Perelman JM, Kolosov VP, et al. Neutrophil elastase induces MUC5AC secretion via protease-activated receptor 2. Mol Cell Biochem 2013;377:75-85.
Excerpt from IUPHAR/BPS Guide to Pharmacology

Related Receptors

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