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Thromb Haemost 2000; 83(05): 639-643
DOI: 10.1055/s-0037-1613883
Review Article
Schattauer GmbH

The Endothelial Cell Protein C Receptor

Charles T. Esmon
1   From the Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Departments of Pathology and Biochemistry and Molecular Biology, University of Oklahoma Health Science Center and Howard Hughes Medical Institute, Oklahoma City, OK, USA
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Publication History

Received 17 December 1999

Accepted 21 December 1999

Publication Date:
08 December 2017 (online)

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  • References

  • 1 Esmon CT. The roles of protein C and thrombomodulin in the regulation of blood coagulation. J Biol Chem 1989; 264: 4743-6.
    PubMedGoogle Scholar
  • 2 Mateo J, Oliver A, Borrell M, Sala N, Fontcuberta J. the EMET Group. Increased risk of venous thrombosis in carriers of natural anticoagulant deficiencies. Results of the family studies of the Spanish Multicenter Study on Thrombophilia (EMET study). Blood Coagul Fibrinol 1998; 09: 71-8.
    CrossrefPubMedGoogle Scholar
  • 3 Lane DA, Mannucci PM, Bauer KA, Bertina RM, Bochkov NP, Boulyjenkov V, Chandy M, Dahlbäck B, Ginter EK, Miletich JP, Rosendaal FR, Seligsohn U. Inherited thrombophilia: Part 2. Thromb Haemost 1996; 76: 824-34.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Norlund L, Zoller B, Öhlin A-K. A novel thrombomodulin gene mutation in a patient suffering from sagittal sinus thrombosis. Thromb Haemost 1997; 78: 1164-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Öhlin A-K, Norlund L, Marlar RA. Thrombomodulin gene variations and thromboembolic disease. Thromb Haemost 1997; 78: 396-400.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Doggen CJM, Cats VM, Bertina RM, Rosendaal FR. Interaction of coagulation defects and cardiovascular risk factors: increased risk of myocardial infarction associated with factor V Leiden or prothrombin 20210A. Circulation 1998; 97: 1037-41.
    CrossrefPubMedGoogle Scholar
  • 7 Rosendaal FR, Siscovick DS, Schwartz SM, Beverly RK, Psaty BM, Longstreth WT, Raghunathan TE, Koepsell TD, Reitsma PH. Factor V Leiden (resistance to activated protein C) increases the risk of myocardial infarction in young women. Blood 1997; 89: 2817-21.
    PubMedGoogle Scholar
  • 8 Norlund L, Holm J, Zoller B, Öhlin A-K. A common thrombomodulin amino acid dimorphism is associated with myocardial infarction. Thromb Haemost 1997; 77: 248-51.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Dittman WA. Thrombomodulin: Biology and potential cardiovascular applications. Trends Cardiovasc Med 1991; 01: 331-6.
    CrossrefPubMedGoogle Scholar
  • 10 Bajzar L, Morser J, Nesheim M. TAFI, or Plasma Procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombinthrombomodulin complex. J Biol Chem 1996; 271: 16603-8.
    CrossrefPubMedGoogle Scholar
  • 11 Bourin MC, Lindahl U. Glycosaminoglycans and the regulation of blood coagulation. Biochem J 1993; 289: 313-30.
    CrossrefPubMedGoogle Scholar
  • 12 Rezaie AR, Cooper ST, Church FC, Esmon CT. Protein C inhibitor is a potent inhibitor of the thrombin-thrombomodulin complex. J Biol Chem 1995; 270: 25336-9.
    CrossrefPubMedGoogle Scholar
  • 13 Esmon NL, DeBault LE, Esmon CT. Proteolytic formation and properties of gamma-carboxyglutamic acid-domainless protein C. J Biol Chem 1983; 258: 5548-53.
    PubMedGoogle Scholar
  • 14 Esmon NL. Thrombomodulin. In: Progress in Hemostasis and Thrombosis, vol. 9. Coller BS. WB Saunders Company; Philadelphia: 1988: 29-58.
    Google Scholar
  • 15 Fukudome K, Esmon CT. Identification, cloning and regulation of a novel endothelial cell protein C/activated protein C receptor. J Biol Chem 1994; 269: 26486-91.
    PubMedGoogle Scholar
  • 16 Bangalore N, Drohan WN, Orthner CL. High affinity binding sites for activated protein C and protein C on cultured human umbilical vein endothelial cells independent of protein S and distinct from known ligands. Thromb Haemost 1994; 72: 465-74.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 O’Regan DJ, Brennand D, Esmon CT, Goodwin CA, Kakkar VV, Scully ME. Specific binding of activated protein C (APC) to vascular smooth muscle cells is not due to the endothelial receptor (EPCR). Blood. 1997 90. 78b (Abstr.).
    PubMedGoogle Scholar
  • 18 Stearns-Kurosawa DJ, Kurosawa S, Mollica JS, Ferrell GL, Esmon CT. The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex. Proc Natl Acad Sci (USA) 1996; 93: 10212-6.
    CrossrefPubMedGoogle Scholar
  • 19 Fukudome K, Ye X, Tsuneyoshi N, Tokunaga O, Sugawara K, Mizokami H, Kimoto M. Activation mechanism of anticoagulant protein C in large blood vessels involving the endothelial cell protein C receptor. J Exp Med 1998; 187: 1029-35.
    CrossrefPubMedGoogle Scholar
  • 20 Xu J, Esmon NL, Esmon CT. Reconstitution of the human endothelial cell protein C receptor with thrombomodulin in phosphatidylcholine vesicles enhances protein C activation. J Biol Chem 1999; 274: 6704-10.
    CrossrefPubMedGoogle Scholar
  • 21 Fukudome K, Kurosawa S, Stearns-Kurosawa DJ, He X, Rezaie AR, Esmon CT. The endothelial cell protein C receptor: Cell surface expression and direct ligand binding by the soluble receptor. J Biol Chem 1996; 271: 17491-8.
    CrossrefPubMedGoogle Scholar
  • 22 Liaw PCY, Neuenschwander PF, Smirnov MD, Esmon CT. Mechanisms by which soluble endothelial cell protein C receptor modulates protein C and activated protein C function. J Biol Chem 2000; 275: 5447-52.
    CrossrefPubMedGoogle Scholar
  • 23 Regan LM, Mollica JS, Rezaie AR, Esmon CT. The interaction between the endothelial cell protein C receptor and protein C is dictated by the Gla domain of protein C. J Biol Chem 1997; 272: 26279-84.
    CrossrefPubMedGoogle Scholar
  • 24 Colpitts TL, Castellino FJ. Calcium and phospholipid binding properties of synthetic gamma-carboxyglutamic acid-containing peptides with sequence counterparts in human protein C. Biochemistry 1994; 33: 3501-8.
    CrossrefPubMedGoogle Scholar
  • 25 Fukudome K, Esmon CT. Molecular cloning and expression of murine and bovine endothelial cell protein C/activated protein C receptor (EPCR). The structural and functional conservation in human, bovine, and murine EPCR. J Biol Chem 1995; 270: 5571-7.
    CrossrefPubMedGoogle Scholar
  • 26 Simmonds RE, Lane DA. Structural and functional implications of the intron/exon organization of the human endothelial cell protein C/activated protein C receptor (EPCR) gene: Comparison with the structure of CD1/major histocompatibility complex a1 and a2 domains. Blood 1999; 94: 632-41.
    PubMedGoogle Scholar
  • 27 Liang Z, Rosen ED, Castellino FJ. Nucleotide structure and characterization of the murine gene encoding the endothelial cell protein C receptor. Thromb Haemost 1999; 81: 585-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Xu J, Liaw PCY, Esmon CT. A novel transmembrane domain of the endothelial cell protein C receptor (EPCR) dictates receptor localization of sphingolipid-cholesterol rich regions on plasma membrane while EPCR palmitoylation modulates intracellular trafficking patterns. Thromb Haemost. (Suppl: Aug 1999): 695 (Abstr.).
    PubMedGoogle Scholar
  • 29 Xu J, Qu D, Esmon CT. Characterization of endothelial protein C receptor. Book of Abstracts, Vascular Biology ‘98 Scientific Conference of American Heart Association and North American Vascular Biology Organization 1998 #61 (Abstr.)
    PubMed
  • 30 Xu J, Esmon DT. Endothelial cell protein C receptor (EPCR) constitutively translocates into the nucleus and also mediates activated protein C, but not protein C, nuclear translocation. Thromb Haemost. (Suppl: Aug 1999): 206 (Abstr.).
    PubMedGoogle Scholar
  • 31 Kurosawa S, Stearns-Kurosawa DJ, Hidari N, Esmon CT. Identification of functional endothelial protein C receptor in human plasma. J Clin Invest 1997; 100: 411-8.
    CrossrefPubMedGoogle Scholar
  • 32 Kurosawa S, Stearns-Kurosawa DJ, Carson CW, D’Angelo A, Della PValle, Esmon CT. Plasma levels of endothelial cell protein C receptor are elevated in patients with sepsis and systemic lupus erythematosus: Lack of correlation with thrombomodulin suggests involvement of different pathological processes. Blood 1998; 91: 725-7.
    PubMedGoogle Scholar
  • 33 Xu J, Qu D, Esmon NL, Esmon CT. Metalloproteolytic release of endothelial cell protein C receptor. J Biol Chem 2000; 275: 6038-44.
    CrossrefPubMedGoogle Scholar
  • 34 Laszik ZG, Ferrell G, Silva FG, Esmon CT. Endothelial protein C receptor (EPCR) and thrombomodulin (TM) are downregulated in coronary atherosclerosis. United States Academy of Pathology (USCAP) Annual Meeting 1999. (In Press).
    PubMedGoogle Scholar
  • 35 Feehan C, Darlak K, Kahn J, Walcheck B, Spatola AF, Kishimoto TK. Shedding of the lymphocyte L-selectin adhesion molecule is inhibited by a hydroxamic acid-based protease inhibitor. J Biol Chem 1996; 271: 7019-24.
    CrossrefPubMedGoogle Scholar
  • 36 Gu J-M, Katsuura Y, Ferrell GL, Grammas P, Esmon CT. Endotoxin and thrombin elevate rodent endothelial cell protein C receptor mRNA levels and increase receptor shedding in vivo. Blood 2000; 95: 1687-93.
    PubMedGoogle Scholar
  • 37 Gu JM, Esmon CT. Characterization and Regulation of the 5’-flanking region of the murine endothelial protein C receptor gene. J Biol Chem. (In press).
    PubMedGoogle Scholar
  • 38 Stearns-Kurosawa DJ, Esmon CT, Kurosawa S. The endothelial protein C receptor, neutrophil, proteinase-3 and Wegener’s granulomatosis. Thromb Haemost. (Suppl: Aug 1999): 215 (Abstr.).
    PubMedGoogle Scholar
  • 39 Kurosawa S, Esmon CT, Stearns-Kurosawa DJ. The soluble endothelial protein C receptor binds to a proteinase-3/MAC-1 heterocomplex on neutrophils. Blood. 1999 94. 648a (Abstr.).
    PubMedGoogle Scholar
  • 40 Regan LM, Stearns-Kurosawa DJ, Kurosawa S, Mollica J, Fukudome K, Esmon CT. The endothelial cell protein C receptor: Inhibition of activated protein C anticoagulant function without modulation of reaction with proteinase inhibitors. J Biol Chem 1996; 271: 17499-503.
    CrossrefPubMedGoogle Scholar
  • 41 Laszik Z, Mitro A, Taylor FB, Ferrell Jr G, Esmon CT. Human protein C receptor is present primarily on endothelium of large blood vessels: Implications for the control of the protein C pathway. Circulation 1997; 96: 3633-40.
    CrossrefPubMedGoogle Scholar
  • 42 Ye X, Fukudome K, Tsuneyoshi N, Satoh T, Tokunaga O, Sugawara K, Mizokami H, Kimoto M. The endothelial cell protein C receptor (EPCR) functions as a primary receptor for protein C activation on endothelial cells in arteries, veins, and capillaries. Biochem Biophys Res Commun 1999; 259: 671-7.
    CrossrefPubMedGoogle Scholar
  • 43 Taylor Jr FB, Chang A, Esmon CT, D’Angelo A, Vigano-D’Angelo S, Blick KE. Protein C prevents the coagulopathic and lethal effects of E. coli infusion in the baboon. J Clin Invest 1987; 79: 918-25.
    CrossrefPubMedGoogle Scholar
  • 44 Taylor Jr FB, Stearns-Kurosawa DJ, Kurosawa S, Ferrell G, Chang A, Laszik Z, Kosanke S, Peer G, Esmon CT. The endothelial cell protein C receptor aids in host defense against E. coli sepsis. Blood 2000; 95: 1680-6.
    PubMedGoogle Scholar
  • 45 Faust SN, Heyderman RS, Harrison O, Goldin RD, Laszik Z, Esmon CT, Levin M. Molecular mechanisms of thrombosis in meningococcal septicaemia: the role of the protein C pathway in vivo. 2nd Annual Meeting of the British Infection Society, London (Abstr.), 1999.
    PubMed
  • 46 Merati G, Biguzzi E, Oganesyan N, Fetiveau R, Qu DF, Bucciarelli P, Stearns DJ, Mannucci PM, Esmon CT, Faioni EM. A 23bp insertion in the endothelial protein C receptor (EPCR) gene in patients with myocardial infarction and deep vein thrombosis. Thromb Haemost. (Suppl: Aug 1999): 507 (Abstr.), 1999.
    PubMedGoogle Scholar