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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3442-3451. Prepublished online as a Blood First Edition Paper on December 11, 2007; DOI 10.1182/blood-2007-08-104968. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-08-104968v1 111/7/3442    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Saposnik, B. Articles by Gandrille, S. Search for Related Content PubMed PubMed Citation Articles by Saposnik, B. Articles by Gandrille, S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Alternative mRNA is favored by the A3 haplotype of the EPCR gene PROCR and generates a novel soluble form of EPCR in plasma Beatrice Saposnik1,4, Elodie Lesteven1, Anna Lokajczyk1,2, Charles T. Esmon5, Martine Aiach1,3, and Sophie Gandrille1,3 1 Inserm U765, Paris, France; 2 Université Paris Descartes, Unité de Formation et de Recherche (UFR) des Sciences Pharmaceutiques, Paris, France; 3 Assistance Publique-Hôpitaux de Paris (AP-HP), Hopital Européen Georges Pompidou, Service d'Hématologie biologique A, Paris, France; 4 AP-HP, Hôpital Robert Debré, Service d'Hématologie biologique, Paris, France; and 5 Howard Hughes Medical Institute and Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK The endothelial cell protein C receptor also exists in soluble form in plasma (sEPCR), resulting from ADAM17 cleavage. Elevated sEPCR levels are observed in subjects carrying the A3 haplotype, which is characterized by a Ser219Gly substitution in the transmembrane domain, rendering the receptor more sensitive to cleavage. Because sEPCR production is not completely blocked by metalloprotease inhibition, we looked for another mechanism. Comparing mRNA expression patterns and levels in A3 and non-A3 cells from 32 human umbilical cord veins, we detected a truncated mRNA in addition to the full-length mRNA. This truncated mRNA was 16 times more abundant in A3 human umbilical vein endothelial cells than in non-A3 human umbilical vein endothelial cells and encoded a protein lacking the transmembrane domain. We stably expressed a recombinant form of this protein (rEPCRisoform) and a protein mimicking the plasma sEPCR (rEPCRsol). Functional studies of the purified recombinant proteins revealed that the rEPCRisoform bound to recombinant protein C with similar affinity than rEPCRsol and that it also inhibited the anticoagulant activity of APC. Trace amounts of the EPCR isoform were found in the plasma of A3 subjects. These results suggest that the sEPCRisoform could contribute to the regulatory effect of sEPCR in plasma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Soluble protein C receptor: why? Margarethe Geiger Blood 2008 111: 3301-3302. [Full Text] [PDF] This article has been cited by other articles: S. Gandrille Endothelial cell protein C receptor and the risk of venous thrombosis Haematologica, June 1, 2008; 93(6): 812 - 816. [Full Text] [PDF] E. Molina, J. Hermida, J. Lopez-Sagaseta, C. Puy, and R. Montes The functional properties of a truncated form of endothelial cell protein C receptor generated by alternative splicing Haematologica, June 1, 2008; 93(6): 878 - 884. [Abstract] [Full Text] [PDF]

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