title: Protease-activated receptor 4: a critical participator in inflammatory response.
abstract: Protease-activated receptors (PARs) are G protein-coupled receptors of which four members PAR1, PAR2, PAR3, and PAR4 have been identified, characterized by a typical mechanism of activation involving various related proteases. The amino-terminal sequence of PARs is cleaved by a broad array of proteases, leading to specific proteolytic cleavage which forms endogenous tethered ligands to induce agonist-biased PAR activation. The biological effect of PARs activated by coagulation proteases to regulate hemostasis and thrombosis plays an enormous role in the cardiovascular system, while PAR4 can also be activated by trypsin, cathepsin G, the activated factor X of the coagulation cascade, and trypsin IV. Irrespective of its role in thrombin-induced platelet aggregation, PAR4 activation is believed to be involved in inflammatory lesions, as show by investigations that have unmasked the effects of PAR4 on neutrophil recruitment, the regulation of edema, and plasma extravasation. This review summarizes the roles of PAR4 in coagulation and other extracellular protease pathways, which activate PAR4 to participate in normal regulation and disease.
authors.affiliation: Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, 450008, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.forename: Yebo
authors.initials: Y
authors.lastname: Gao
authors.forename: Yonglei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Chen
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xie
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D010447:Peptide Hydrolases / Q000276:immunology / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000276:immunology / Q000378:metabolism; D018179:Receptors, Thrombin / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D043562:Receptors, G-Protein-Coupled; D018179:Receptors, Thrombin; D010447:Peptide Hydrolases; C112908:protease-activated receptor 4