Regulation of Blood Coagulation by the Protein C Anticoagulant Pathway. Novel Insights Into Structure-Function Relationships and Molecular Recognition.
(2005) In Arteriosclerosis, Thrombosis and Vascular Biology 25(7). p.1311-1320- Abstract
- The protein C system provides important control of blood coagulation by regulating the activities of factor VIIIa (FVIIIa) and factor Va(FVa), cofactors in the activation of factor X and prothrombin, respectively. The system comprises membrane-bound and circulating proteins that assemble into multi-molecular complexes on cell surfaces. Vitamin K-dependent protein C, the key component of the system, circulates in blood as zymogen to an anticoagulant serine protease. It is efficiently activated on the surface of endothelial cells by thrombin bound to the membrane protein thrombomodulin. The endothelial protein C receptor (EPCR) further stimulates the protein C activation. Activated protein C (APC) together with its cofactor protein S... (More)
- The protein C system provides important control of blood coagulation by regulating the activities of factor VIIIa (FVIIIa) and factor Va(FVa), cofactors in the activation of factor X and prothrombin, respectively. The system comprises membrane-bound and circulating proteins that assemble into multi-molecular complexes on cell surfaces. Vitamin K-dependent protein C, the key component of the system, circulates in blood as zymogen to an anticoagulant serine protease. It is efficiently activated on the surface of endothelial cells by thrombin bound to the membrane protein thrombomodulin. The endothelial protein C receptor (EPCR) further stimulates the protein C activation. Activated protein C (APC) together with its cofactor protein S inhibits coagulation by degrading FVIIIa and FVa on the surface of negatively charged phospholipid membranes. Efficient FVIIIa degradation by APC requires not only protein S but also intact FV, which like thrombin is a Janus-faced protein with both procoagulant and anticoagulant potential. In addition to its anticoagulant properties, APC has antiinflammatory and antiapoptotic functions, which are exerted when APC binds to EPCR and proteolytic cleaves protease-activated receptor 1 (PAR-1). The protein C system is physiologically important, and genetic defects affecting the system are the most common risk factors of venous thrombosis. The proteins of the protein C system are composed of multiple domains and the 3-dimensional structures of several of the proteins are known. The molecular recognition of the protein C system is progressively being unraveled, giving us new insights into this fascinating and intricate molecular scenario at the atomic level. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/138256
- author
- Dahlbäck, Björn LU and Villoutreix, Bruno O
- organization
- publishing date
- 2005
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- thrombomodulin, factor V, protein C, protein S
- in
- Arteriosclerosis, Thrombosis and Vascular Biology
- volume
- 25
- issue
- 7
- pages
- 1311 - 1320
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- wos:000230112200004
- pmid:15860736
- scopus:21544447526
- ISSN
- 1524-4636
- DOI
- 10.1161/01.ATV.0000168421.13467.82
- language
- English
- LU publication?
- yes
- id
- b065f81f-6cd4-4608-b75f-6612e9b82d2b (old id 138256)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15860736&dopt=Abstract
- date added to LUP
- 2016-04-01 11:54:36
- date last changed
- 2022-05-06 19:01:15
@article{b065f81f-6cd4-4608-b75f-6612e9b82d2b,
abstract = {{The protein C system provides important control of blood coagulation by regulating the activities of factor VIIIa (FVIIIa) and factor Va(FVa), cofactors in the activation of factor X and prothrombin, respectively. The system comprises membrane-bound and circulating proteins that assemble into multi-molecular complexes on cell surfaces. Vitamin K-dependent protein C, the key component of the system, circulates in blood as zymogen to an anticoagulant serine protease. It is efficiently activated on the surface of endothelial cells by thrombin bound to the membrane protein thrombomodulin. The endothelial protein C receptor (EPCR) further stimulates the protein C activation. Activated protein C (APC) together with its cofactor protein S inhibits coagulation by degrading FVIIIa and FVa on the surface of negatively charged phospholipid membranes. Efficient FVIIIa degradation by APC requires not only protein S but also intact FV, which like thrombin is a Janus-faced protein with both procoagulant and anticoagulant potential. In addition to its anticoagulant properties, APC has antiinflammatory and antiapoptotic functions, which are exerted when APC binds to EPCR and proteolytic cleaves protease-activated receptor 1 (PAR-1). The protein C system is physiologically important, and genetic defects affecting the system are the most common risk factors of venous thrombosis. The proteins of the protein C system are composed of multiple domains and the 3-dimensional structures of several of the proteins are known. The molecular recognition of the protein C system is progressively being unraveled, giving us new insights into this fascinating and intricate molecular scenario at the atomic level.}},
author = {{Dahlbäck, Björn and Villoutreix, Bruno O}},
issn = {{1524-4636}},
keywords = {{thrombomodulin; factor V; protein C; protein S}},
language = {{eng}},
number = {{7}},
pages = {{1311--1320}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Arteriosclerosis, Thrombosis and Vascular Biology}},
title = {{Regulation of Blood Coagulation by the Protein C Anticoagulant Pathway. Novel Insights Into Structure-Function Relationships and Molecular Recognition.}},
url = {{http://dx.doi.org/10.1161/01.ATV.0000168421.13467.82}},
doi = {{10.1161/01.ATV.0000168421.13467.82}},
volume = {{25}},
year = {{2005}},
}