Proteinase-activated receptor 2 (PAR2) (PAR2)

Proteinase-activated receptor 2 (PAR2), encoded by the F2RL1 gene, is a G protein-coupled receptor that plays a pivotal role in regulating epithelial and endothelial barrier function through the tight junction regulatory pathway (Source: UniProt P55085). Unlike traditional receptors, PAR2 is activated when serine proteases, such as trypsin or mast cell tryptase, cleave its extracellular N-terminus to reveal a tethered ligand. This activation triggers signaling cascades, including the Gq/11 and Rho pathways, which modulate the assembly and maintenance of tight junction proteins like zonula occludens-1 (ZO-1), occludin, and claudins (Source: PMID: 25608265). In pathological states such as inflammatory bowel disease (IBD), asthma, and atopic dermatitis, overactivation of PAR2 leads to increased paracellular permeability and barrier breakdown (Source: PMID: 30107159). Therapeutic strategies targeting this pathway involve PAR2 antagonists, pepducins, or protease inhibitors to prevent the disruption of tight junctions and restore tissue homeostasis. Research into PAR2-mediated barrier regulation continues to highlight its potential as a target for treating chronic inflammatory and allergic conditions.

Other names

F2RL1Coagulation factor II receptor-like 1Thrombin receptor-like 1G-protein coupled receptor 11PAR-2

Antagonism of the receptor or inhibition of the activating proteases to prevent N-terminal cleavage and subsequent signaling that disrupts tight junction integrity.