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

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 brady...

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Autores principales: Motta, Guacyara, Juliano, Luiz, Chagas, Jair Ribeiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10499198/
https://www.ncbi.nlm.nih.gov/pubmed/37711466
http://dx.doi.org/10.3389/fphys.2023.1188816
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author Motta, Guacyara
Juliano, Luiz
Chagas, Jair Ribeiro
author_facet Motta, Guacyara
Juliano, Luiz
Chagas, Jair Ribeiro
author_sort Motta, Guacyara
collection PubMed
description 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.
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spelling pubmed-104991982023-09-14 Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond Motta, Guacyara Juliano, Luiz Chagas, Jair Ribeiro Front Physiol Physiology 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. Frontiers Media S.A. 2023-08-30 /pmc/articles/PMC10499198/ /pubmed/37711466 http://dx.doi.org/10.3389/fphys.2023.1188816 Text en Copyright © 2023 Motta, Juliano and Chagas. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Motta, Guacyara
Juliano, Luiz
Chagas, Jair Ribeiro
Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond
title Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond
title_full Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond
title_fullStr Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond
title_full_unstemmed Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond
title_short Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond
title_sort human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10499198/
https://www.ncbi.nlm.nih.gov/pubmed/37711466
http://dx.doi.org/10.3389/fphys.2023.1188816
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