Phosphatidylcholine in the groove of endothelial cell protein C receptor (EPCR) regulates EPCR conformation and protein C recognition

2018 ◽  
Vol 10 (11) ◽  
pp. 696-704 ◽  
Author(s):  
Ramesh Prasad ◽  
Prosenjit Sen
Keyword(s):  
Endothelial Cell ◽  
Complex Formation ◽  
Protein C ◽  
Regulatory Role ◽  
Cell Protein ◽  
Dependent Protein

Lipid-dependent protein C–EPCR complex formation explains the regulatory role of antigenic lipid within the EPCR groove.

Role of a 23 bp Insertion in Exon 3 of the Endothelial Cell Protein C Receptor Gene in Venous Thrombophilia

2002 ◽  
pp. 278-282
Author(s):  
M. Von Depka Prondzinski ◽  
A. Czwalinna ◽  
R. Eisert ◽  
C. Wermes ◽  
B. Canepa ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Protein C ◽  
Receptor Gene ◽  
Cell Protein

Laboratory Issues in Diagnosing Abnormalities of Protein C, Thrombomodulin, and Endothelial Cell Protein C Receptor

2002 ◽  
Vol 126 (11) ◽  
pp. 1337-1348 ◽  
Author(s):  
Kandice Kottke-Marchant ◽  
Philip Comp
Keyword(s):  
Endothelial Cell ◽  
Protein C ◽  
Medical Literature ◽  
Majority Vote ◽  
Diagnostic Testing ◽  
Laboratory Evaluation ◽  
Cell Protein ◽  
Endothelial Protein C Receptor ◽  
Protein C Deficiency

Abstract Objective.—To review the current understanding of the pathophysiology of protein C deficiency and its role in congenital thrombophilia. Recommendations for diagnostic testing for protein C function and concentration, derived from the medical literature and consensus opinions of recognized experts in the field, are included, specifying whom, how, and when to test. The role of related proteins, such as thrombomodulin and endothelial protein C receptor, is also reviewed. Data Sources.—Review of the published medical literature. Data Extraction and Synthesis.—A summary of the medical literature and proposed testing recommendations were prepared and presented at the College of American Pathologists Conference XXXVI: Diagnostic Issues in Thrombophilia. After discussion at the conference, consensus recommendations presented in this manuscript were accepted after a two-thirds majority vote by the participants. Conclusions.—Protein C deficiency is an uncommon genetic abnormality that may be a contributing cause of thrombophilia, often in conjunction with other genetic or acquired risk factors. When assay of protein C plasma levels is included in the laboratory evaluation of thrombophilia, a functional amidolytic protein C assay should be used for initial testing. The diagnosis of protein C deficiency should be established only after other acquired causes of protein C deficiency are excluded. A low protein C level should be confirmed with a subsequent assay on a new specimen. Antigenic protein C assays may be of benefit in subclassification of the type of protein C deficiency. The role of thrombomodulin and endothelial cell protein C receptor in thrombosis has yet to be clearly established, and diagnostic testing is not recommended at this time.

scholarly journals Inactivation of Factor VIIa by Antithrombin In Vitro, Ex Vivo and In Vivo: Role of Tissue Factor and Endothelial Cell Protein C Receptor

PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e103505 ◽  
Author(s):  
Rit Vatsyayan ◽  
Hema Kothari ◽  
Nigel Mackman ◽  
Usha R. Pendurthi ◽  
L. Vijaya Mohan Rao
Keyword(s):  
Endothelial Cell ◽  
Tissue Factor ◽  
Protein C ◽  
Factor Viia ◽  
Ex Vivo ◽  
Cell Protein

scholarly journals An autoantibody directed against human thrombin anion-binding exosite in a patient with arterial thrombosis: effects on platelets, endothelial cells, and protein C activation

Blood ◽  
1994 ◽  
Vol 84 (6) ◽  
pp. 1843-1850 ◽  
Author(s):  
E Arnaud ◽  
M Lafay ◽  
P Gaussem ◽  
V Picard ◽  
M Jandrot-Perrus ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Arterial Thrombosis ◽  
Protein C ◽  
Receptor Activation ◽  
Anion Binding ◽  
Thrombin Receptor ◽  
Cell Functions ◽  
Human Thrombin

Abstract An autoantibody, developed by a patient with severe and recurrent arterial thrombosis, was characterized to be directed against the anion- binding exosite of thrombin, and inhibited all thrombin interactions requiring this secondary binding site without interfering with the catalytic site. The effect of the antibody was studied on thrombin interactions with platelets and endothelial cells from human umbilical veins (HUVEC). The autoantibody specifically and concentration- dependently inhibited alpha-thrombin-induced platelet activation and prostacyclin (PGI2) synthesis from HUVEC. It had no effect when gamma- thrombin or the thrombin receptor activation peptide SFLLR were the inducers. The effect of the antibody on protein C activation has been studied. The antibody blocked the thrombin-thrombomodulin activation of protein C. The inhibition of the activation was maximal with a low concentration of thrombomodulin. The fact that the autoantibody inhibited concentration-dependent alpha-thrombin-induced platelet and endothelial cell functions emphasizes the crucial role of the anion- binding exosite of thrombin to activate its receptor. In regard to the pathology, the antibody inhibited two vascular processes implicated in thrombin-antithrombotic functions, PGI2 secretion, and protein C activation, which could be implicated in this arterial thrombotic disease.

scholarly journals Identification of the Protein C/Activated Protein C Binding Sites on the Endothelial Cell Protein C Receptor

2000 ◽  
Vol 276 (11) ◽  
pp. 8364-8370 ◽  
Author(s):  
Patricia C. Y. Liaw ◽  
Timothy Mather ◽  
Natalia Oganesyan ◽  
Gary L. Ferrell ◽  
Charles T. Esmon
Keyword(s):  
Endothelial Cell ◽  
Binding Sites ◽  
Protein C ◽  
Activated Protein C ◽  
Cell Protein

scholarly journals Inhibition of staurosporine-induced apoptosis of endothelial cells by activated protein C requires protease-activated receptor-1 and endothelial cell protein C receptor

2003 ◽  
Vol 373 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Laurent O. MOSNIER ◽  
John H. GRIFFIN
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Active Site ◽  
Protein C ◽  
Activated Protein C ◽  
Cell Protein ◽  
Protease Activated Receptor 1 ◽  
Induced Apoptosis ◽  
Apoptotic Effects ◽  
Dose Dependent

In a model of staurosporine-induced apoptosis using EAhy926 endothelial cells, inhibition of apoptosis by activated protein C was dose-dependent and required the enzyme's active site, implicating activated protein C-mediated proteolysis. Consistent with this implication, both protease-activated receptor-1 (PAR-1) and endothelial cell protein C receptor (EPCR) were required for the anti-apoptotic effects of activated protein C.

Endothelial Cell Protein C Receptor Deficiency Attenuates Streptococcus pneumoniae–induced Pleural Fibrosis

2021 ◽  
Vol 64 (4) ◽  
pp. 477-491
Author(s):  
Shiva Keshava ◽  
Jhansi Magisetty ◽  
Torry A. Tucker ◽  
Weshely Kujur ◽  
Sachin Mulik ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Streptococcus Pneumoniae ◽  
Protein C ◽  
Cell Protein ◽  
Pleural Fibrosis

Endotoxin and thrombin elevate rodent endothelial cell protein C receptor mRNA levels and increase receptor shedding in vivo

Blood ◽  
2000 ◽  
Vol 95 (5) ◽  
pp. 1687-1693 ◽  
Author(s):  
Jian-Ming Gu ◽  
Yasuhiro Katsuura ◽  
Gary L. Ferrell ◽  
Paula Grammas ◽  
Charles T. Esmon
Keyword(s):  
Cell Culture ◽  
Septic Shock ◽  
Endothelial Cell ◽  
Protein C ◽  
Fold Increase ◽  
Cell Protein ◽  
Thrombin Inhibitor ◽  
Mrna Levels ◽  
Soluble Epcr

The endothelial cell protein C receptor (EPCR) facilitates protein C activation by the thrombin-thrombomodulin complex. Protein C activation has been shown to be critical to the host defense against septic shock. In cell culture, tumor necrosis factor- (TNF-) down-regulates EPCR expression, raising the possibility that EPCR might be down-regulated in septic shock. We examined EPCR mRNA and soluble EPCR levels in mice and rats challenged with lethal dose 95 levels of endotoxin. Toxic doses of TNF- failed to alter EPCR mRNA levels in mice. Rather than EPCR mRNA levels falling in response to endotoxin, as predicted from cell-culture experiments, they rose approximately 3-fold 6 hours after exposure to endotoxin before returning toward baseline levels at 24 hours after exposure. Soluble EPCR levels rose approximately 4-fold. Infusion of hirudin, a specific thrombin inhibitor, before endotoxin exposure almost completely blocked the increase in EPCR mRNA and soluble EPCR. Consistent with the idea that the responses were mediated by thrombin, thrombin infusion (5 U/kg of body weight for 3 hours) resulted in an approximately 2-fold increase in EPCR mRNA and soluble EPCR. Incubation of rat endothelial cells with thrombin or murine protease-activated receptor 1 agonist peptide resulted in a 2-fold increase in EPCR mRNA. These results indicate that thrombin plays a major role in up-regulating EPCR mRNA and shedding in vivo.

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