PAR2

Protease Activated Receptor 2 (PAR2) is a self-activated G protein-coupled receptor and a cell surface receptor for trypsin-like proteases^[1][2]. Mechanistically, proteolytic cleavage exposes a tethered ligand, and PAR2 activation engages Gαq-mediated calcium release, MAPK/ERK1/2 signaling, NFκB, AP1, Smad2, and β-arrestin-related pathways^[1][3][4]. In human kidney tubular epithelial cells, PAR2 activation induces TNF, CSF2, MMP-9, PAI-1, and CTGF, supporting inflammatory and fibrotic pathway studies^[3]. In glioblastoma cell lines, PAR2, but not PAR1, increased VEGF secretion through MAPK/ERK1/2 rather than PI3K/Akt signaling, highlighting isoform-specific experimental relevance^[4]. In epithelial barrier models, PAR2 activation impaired keratinocyte tight junction integrity and reduced claudin-1, occludin, and ZO-1 expression^[5]. Compared with PAR1 and PAR4, PAR2 requires distinct ligand and pathway evaluation because ligands can signal through multiple PAR2 pathways^[1]. For experimental applications, PAR2 agonist peptides, radiolabeled 2-furoyl-LIGRL-NH2, antagonists, antibodies, and pepducins help define receptor activation, binding, selectivity, and inflammatory responses^[1][6][7].