Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond

Frontiers in Physiology

Physiology

Luiz Juliano¹  Jair Ribeiro Chagas¹  Guacyara Motta² 

[1] Departamento de Biofisica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil;Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil;

关键词: bradykinin;    kininogen;    kallikrein;    proteolysis;    cell biology;    inflammation;    inhibitors;   

DOI  :  10.3389/fphys.2023.1188816

 received in 2023-03-17, accepted in 2023-08-15,  发布年份 2023

来源: Frontiers

【 摘 要 】

Human plasma kallikrein (PKa) is obtained by activating its precursor, prekallikrein (PK), historically named the Fletcher factor. Human PKa and tissue kallikreins are serine proteases from the same family, having high- and low-molecular weight kininogens (HKs and LKs) as substrates, releasing bradykinin (Bk) and Lys-bradykinin (Lys-Bk), respectively. This review presents a brief history of human PKa with details and recent observations of its evolution among the vertebrate coagulation proteins, including the relations with Factor XI. We explored the role of Factor XII in activating the plasma kallikrein–kinin system (KKS), the mechanism of activity and control in the KKS, and the function of HK on contact activation proteins on cell membranes. The role of human PKa in cell biology regarding the contact system and KSS, particularly the endothelial cells, and neutrophils, in inflammatory processes and infectious diseases, was also approached. We examined the natural plasma protein inhibitors, including a detailed survey of human PKa inhibitors’ development and their potential market.

【 授权许可】

Unknown   
Copyright © 2023 Motta, Juliano and Chagas.