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Protease‐activated receptors: An illustrated review

Proteases are important regulators of cell behavior, survival, and apoptosis. They communicate to cells directly through a special class of G‐protein–coupled receptors known as protease‐activated receptors (PARs). N‐terminal PAR proteolysis unmasks a neo‐N‐terminus, which serves as a tethered ligand...

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Autores principales: Han, Xu, Nieman, Marvin T., Kerlin, Bryce A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845062/
https://www.ncbi.nlm.nih.gov/pubmed/33537526
http://dx.doi.org/10.1002/rth2.12454
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author Han, Xu
Nieman, Marvin T.
Kerlin, Bryce A.
author_facet Han, Xu
Nieman, Marvin T.
Kerlin, Bryce A.
author_sort Han, Xu
collection PubMed
description Proteases are important regulators of cell behavior, survival, and apoptosis. They communicate to cells directly through a special class of G‐protein–coupled receptors known as protease‐activated receptors (PARs). N‐terminal PAR proteolysis unmasks a neo‐N‐terminus, which serves as a tethered ligand to activate PARs. Using this unique irreversible activation mechanism, PARs relay information across cell membranes. The year 2020 is the 30th year since discovery of the first member of this family, PAR1. In this illustrated review, we highlight achievements in the PAR field over the past 3 decades. Additionally, the known expression profiles of PARs in human tissues and across species are portrayed. We also illustrate the tethered ligand activation mechanism, which is unique to PARs, and PAR regulatory mechanisms. PAR1 was originally named “thrombin receptor” because thrombin was the first protease identified to activate PAR1. However, over the past 30 years, a growing number of proteases have been found to cleave PARs and trigger differential downstream signaling depending on cleavage site, cell type, and species. We exemplify the diversity of PAR1‐mediated signaling outcomes in platelets and endothelial cells as pertinent examples to the hemostasis, thrombosis, and vascular biology fields. Further, the termination and regulation of PAR signaling via endocytosis and currently available pharmacologic approaches are depicted. We conclude with portrayal of clinically translational aspects of PAR biology including pharmacologic manipulation and single‐nucleotide polymorphisms.
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spelling pubmed-78450622021-02-02 Protease‐activated receptors: An illustrated review Han, Xu Nieman, Marvin T. Kerlin, Bryce A. Res Pract Thromb Haemost Illustrated Review Proteases are important regulators of cell behavior, survival, and apoptosis. They communicate to cells directly through a special class of G‐protein–coupled receptors known as protease‐activated receptors (PARs). N‐terminal PAR proteolysis unmasks a neo‐N‐terminus, which serves as a tethered ligand to activate PARs. Using this unique irreversible activation mechanism, PARs relay information across cell membranes. The year 2020 is the 30th year since discovery of the first member of this family, PAR1. In this illustrated review, we highlight achievements in the PAR field over the past 3 decades. Additionally, the known expression profiles of PARs in human tissues and across species are portrayed. We also illustrate the tethered ligand activation mechanism, which is unique to PARs, and PAR regulatory mechanisms. PAR1 was originally named “thrombin receptor” because thrombin was the first protease identified to activate PAR1. However, over the past 30 years, a growing number of proteases have been found to cleave PARs and trigger differential downstream signaling depending on cleavage site, cell type, and species. We exemplify the diversity of PAR1‐mediated signaling outcomes in platelets and endothelial cells as pertinent examples to the hemostasis, thrombosis, and vascular biology fields. Further, the termination and regulation of PAR signaling via endocytosis and currently available pharmacologic approaches are depicted. We conclude with portrayal of clinically translational aspects of PAR biology including pharmacologic manipulation and single‐nucleotide polymorphisms. John Wiley and Sons Inc. 2020-12-06 /pmc/articles/PMC7845062/ /pubmed/33537526 http://dx.doi.org/10.1002/rth2.12454 Text en © 2020 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH). This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Illustrated Review
Han, Xu
Nieman, Marvin T.
Kerlin, Bryce A.
Protease‐activated receptors: An illustrated review
title Protease‐activated receptors: An illustrated review
title_full Protease‐activated receptors: An illustrated review
title_fullStr Protease‐activated receptors: An illustrated review
title_full_unstemmed Protease‐activated receptors: An illustrated review
title_short Protease‐activated receptors: An illustrated review
title_sort protease‐activated receptors: an illustrated review
topic Illustrated Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845062/
https://www.ncbi.nlm.nih.gov/pubmed/33537526
http://dx.doi.org/10.1002/rth2.12454
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