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Protease-Activated Receptor 4: A Critical Participator in Inflammatory Response

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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.

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Authors and Affiliations

  1. Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, 450008, China

    Qiang Fu, Yonglei Zhang, Xiaobing Chen & Jianguo Xie

  2. Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450007, China

    Jing Cheng

  3. Guang’anmen Hospital, China Academy of Chinese Medical Science, Beijing, 100053, China

    Yebo Gao

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  1. Qiang Fu
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Correspondence to Jianguo Xie.

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Qiang Fu and Jing Cheng are co-first authors; they contributed equally to the work.

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Fu, Q., Cheng, J., Gao, Y. et al. Protease-Activated Receptor 4: A Critical Participator in Inflammatory Response. Inflammation 38, 886–895 (2015). https://doi.org/10.1007/s10753-014-9999-6

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