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PROCR  -  protein C receptor, endothelial

Homo sapiens

Synonyms: APC receptor, Activated protein C receptor, CCCA, CCD41, CD201, ...
 
 
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Disease relevance of PROCR

  • In addition, we detected EPCR expression in tumor cells from breast cancer patients, with an extremely high frequency [1].
  • In the last years, several reports have suggested the association between mutations in TM and EPCR genes and venous and arterial thrombosis [2].
  • These data suggest that novel EPCR ligation and S1P1 transactivation results in EC cytoskeletal rearrangement and barrier protection, components potentially critical to the improved survival of APC-treated patients with severe sepsis [3].
  • Influence of the 4600A/G and 4678G/C polymorphisms in the endothelial protein C receptor (EPCR) gene on the risk of venous thromboembolism in carriers of factor V Leiden [4].
  • Prevalence of a 23bp insertion in exon 3 of the endothelial cell protein C receptor gene in venous thrombophilia [5].
 

High impact information on PROCR

  • Cytoprotection of brain endothelium by APC in vitro required endothelial protein C receptor (EPCR) and protease-activated receptor-1 (PAR-1), as did its in vivo neuroprotective activity in a stroke model of mice with a severe deficiency of EPCR [6].
  • By these mechanisms, EPCR appears to enable significant levels of protein C activation in large vessels [7].
  • In vitro cultured, arterial endothelial cells were also found to express abundant EPCR and were capable of promoting significant levels of protein C activation [7].
  • Flow cytometry experiments demonstrated that plasma EPCR bound APC with an affinity similar to that previously determined for recombinant soluble EPCR (Kdapp = 30 nM) [8].
  • The liver sinusoids were the only capillaries in which EPCR was expressed at moderate levels and thrombomodulin was low [9].
 

Biological context of PROCR

 

Anatomical context of PROCR

 

Associations of PROCR with chemical compounds

 

Physical interactions of PROCR

 

Regulatory relationships of PROCR

 

Other interactions of PROCR

  • The messenger RNA levels of TM and EPCR were determined by real-time polymerase chain reaction [12].
  • The cells treated with CRP (10 and 25 microg/mL) showed significant reductions of EPCR mRNA levels by 34% and 33%, respectively (P < .05) [12].
  • Once APC dissociates from EPCR, it binds to protein S on appropriate cell surfaces where it inactivates factors Va and VIIIa, thereby inhibiting further thrombin generation [24].
  • A monoclonal antibody, RCR252, which blocks APC binding to EPCR, or a blocking antibody to PAR-1, abolished APC's effects on keratinocytes [25].
  • The endothelial cell protein C receptor. Inhibition of activated protein C anticoagulant function without modulation of reaction with proteinase inhibitors [26].
 

Analytical, diagnostic and therapeutic context of PROCR

References

  1. Expression and anticoagulant function of the endothelial cell protein C receptor (EPCR) in cancer cell lines. Tsuneyoshi, N., Fukudome, K., Horiguchi, S., Ye, X., Matsuzaki, M., Toi, M., Suzuki, K., Kimoto, M. Thromb. Haemost. (2001) [Pubmed]
  2. Inherited abnormalities in the protein C activation pathway. España, F., Medina, P., Navarro, S., Estellés, A., Aznar, J. Pathophysiol. Haemost. Thromb. (2002) [Pubmed]
  3. Activated protein C mediates novel lung endothelial barrier enhancement: role of sphingosine 1-phosphate receptor transactivation. Finigan, J.H., Dudek, S.M., Singleton, P.A., Chiang, E.T., Jacobson, J.R., Camp, S.M., Ye, S.Q., Garcia, J.G. J. Biol. Chem. (2005) [Pubmed]
  4. Influence of the 4600A/G and 4678G/C polymorphisms in the endothelial protein C receptor (EPCR) gene on the risk of venous thromboembolism in carriers of factor V Leiden. Medina, P., Navarro, S., Estellés, A., Vayá, A., Bertina, R.M., España, F. Thromb. Haemost. (2005) [Pubmed]
  5. Prevalence of a 23bp insertion in exon 3 of the endothelial cell protein C receptor gene in venous thrombophilia. von Depka, M., Czwalinna, A., Eisert, R., Wermes, C., Scharrer, I., Ganser, A., Ehrenforth, S. Thromb. Haemost. (2001) [Pubmed]
  6. Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective. Cheng, T., Liu, D., Griffin, J.H., Fernández, J.A., Castellino, F., Rosen, E.D., Fukudome, K., Zlokovic, B.V. Nat. Med. (2003) [Pubmed]
  7. Activation mechanism of anticoagulant protein C in large blood vessels involving the endothelial cell protein C receptor. Fukudome, K., Ye, X., Tsuneyoshi, N., Tokunaga, O., Sugawara, K., Mizokami, H., Kimoto, M. J. Exp. Med. (1998) [Pubmed]
  8. Identification of functional endothelial protein C receptor in human plasma. Kurosawa, S., Stearns-Kurosawa, D.J., Hidari, N., Esmon, C.T. J. Clin. Invest. (1997) [Pubmed]
  9. Human protein C receptor is present primarily on endothelium of large blood vessels: implications for the control of the protein C pathway. Laszik, Z., Mitro, A., Taylor, F.B., Ferrell, G., Esmon, C.T. Circulation (1997) [Pubmed]
  10. Identification of the protein C/activated protein C binding sites on the endothelial cell protein C receptor. Implications for a novel mode of ligand recognition by a major histocompatibility complex class 1-type receptor. Liaw, P.C., Mather, T., Oganesyan, N., Ferrell, G.L., Esmon, C.T. J. Biol. Chem. (2001) [Pubmed]
  11. Identification, cloning, and regulation of a novel endothelial cell protein C/activated protein C receptor. Fukudome, K., Esmon, C.T. J. Biol. Chem. (1994) [Pubmed]
  12. C-reactive protein decreases expression of thrombomodulin and endothelial protein C receptor in human endothelial cells. Nan, B., Yang, H., Yan, S., Lin, P.H., Lumsden, A.B., Yao, Q., Chen, C. Surgery (2005) [Pubmed]
  13. Coagulation and inflammation. Esmon, C.T. J. Endotoxin Res. (2003) [Pubmed]
  14. The endothelial cell protein C receptor (EPCR) functions as a primary receptor for protein C activation on endothelial cells in arteries, veins, and capillaries. Ye, X., Fukudome, K., Tsuneyoshi, N., Satoh, T., Tokunaga, O., Sugawara, K., Mizokami, H., Kimoto, M. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  15. Human vascular smooth muscle cells express functionally active endothelial cell protein C receptor. Bretschneider, E., Uzonyi, B., Weber, A.A., Fischer, J.W., Pape, R., Lötzer, K., Schrör, K. Circ. Res. (2007) [Pubmed]
  16. The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex. Stearns-Kurosawa, D.J., Kurosawa, S., Mollica, J.S., Ferrell, G.L., Esmon, C.T. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  17. Reconstitution of the human endothelial cell protein C receptor with thrombomodulin in phosphatidylcholine vesicles enhances protein C activation. Xu, J., Esmon, N.L., Esmon, C.T. J. Biol. Chem. (1999) [Pubmed]
  18. Metalloproteolytic release of endothelial cell protein C receptor. Xu, J., Qu, D., Esmon, N.L., Esmon, C.T. J. Biol. Chem. (2000) [Pubmed]
  19. Recombinant human activated protein C upregulates cyclooxygenase-2 expression in endothelial cells via binding to endothelial cell protein C receptor and activation of protease-activated receptor-1. Brueckmann, M., Horn, S., Lang, S., Fukudome, K., Schulze Nahrup, A., Hoffmann, U., Kaden, J.J., Borggrefe, M., Haase, K.K., Huhle, G. Thromb. Haemost. (2005) [Pubmed]
  20. Mechanisms by which soluble endothelial cell protein C receptor modulates protein C and activated protein C function. Liaw, P.C., Neuenschwander, P.F., Smirnov, M.D., Esmon, C.T. J. Biol. Chem. (2000) [Pubmed]
  21. The anticoagulant protein C pathway. Dahlbäck, B., Villoutreix, B.O. FEBS Lett. (2005) [Pubmed]
  22. The soluble endothelial protein C receptor binds to activated neutrophils: involvement of proteinase-3 and CD11b/CD18. Kurosawa, S., Esmon, C.T., Stearns-Kurosawa, D.J. J. Immunol. (2000) [Pubmed]
  23. Anti-inflammatory effect of activated protein C in gastric epithelial cells. Nakamura, M., Gabazza, E.C., Imoto, I., Yano, Y., Taguchi, O., Horiki, N., Fukudome, K., Suzuki, K., Adachi, Y. J. Thromb. Haemost. (2005) [Pubmed]
  24. The protein C pathway. Esmon, C.T. Chest (2003) [Pubmed]
  25. Endothelial protein C receptor and protease-activated receptor-1 mediate induction of a wound-healing phenotype in human keratinocytes by activated protein C. Xue, M., Campbell, D., Sambrook, P.N., Fukudome, K., Jackson, C.J. J. Invest. Dermatol. (2005) [Pubmed]
  26. The endothelial cell protein C receptor. Inhibition of activated protein C anticoagulant function without modulation of reaction with proteinase inhibitors. Regan, L.M., Stearns-Kurosawa, D.J., Kurosawa, S., Mollica, J., Fukudome, K., Esmon, C.T. J. Biol. Chem. (1996) [Pubmed]
 
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