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Blood, 1 June 2007, Vol. 109, No. 11, pp. 4769-4776. Prepublished online as a Blood First Edition Paper on March 1, 2007; DOI 10.1182/blood-2006-09-046953. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-09-046953v1 109/11/4769    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 Malleier, J. M. Articles by Geiger, M. Search for Related Content PubMed PubMed Citation Articles by Malleier, J. M. Articles by Geiger, M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Regulation of protein C inhibitor (PCI) activity by specific oxidized and negatively charged phospholipids Julia M. Malleier1, Olga Oskolkova1, Valery Bochkov1, Ingrid Jerabek1, Barbora Sokolikova1, Thomas Perkmann1, Johannes Breuss1, Bernd R. Binder1, and Margarethe Geiger1 1 Department of Vascular Biology and Thrombosis Research, Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria Protein C inhibitor (PCI) is a serpin with affinity for heparin and phosphatidylethanolamine (PE). We analyzed the interaction of PCI with different phospholipids and their oxidized forms. PCI bound to oxidized PE (OxPE), and oxidized and unoxidized phosphatidylserine (PS) immobilized on microtiter plates and in aqueous suspension. Binding to OxPE and PS was competed by heparin, but not by the aminophospholipid-binding protein annexin V or the PCI-binding lipid retinoic acid. PS and OxPE stimulated the inhibition of activated protein C (aPC) by PCI in a Ca++-dependent manner, indicating that binding of both, aPC (Ca++ dependent) and PCI (Ca++ independent), to phospholipids is necessary. A peptide corresponding to the heparin-binding site of PCI abolished the stimulatory effect of PS on aPC inhibition. No stimulatory effect of phospholipids on aPC inhibition was seen with a PCI mutant lacking the heparin-binding site. A heparin-like effect of phospholipids (OxPE) was not seen with antithrombin III, another heparin-binding serpin, suggesting that it is specific for PCI. PCI and annexin V were found to be endogenously colocalized in atherosclerotic plaques, supporting the hypothesis that exposure of oxidized PE and/or PS may be important for the local regulation of PCI activity in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. Sun, S. Parry, M. Panico, H. R. Morris, M. Kjellberg, A. Engstrom, A. Dell, and S. Schedin-Weiss N-Glycans and the N Terminus of Protein C Inhibitor Affect the Cofactor-enhanced Rates of Thrombin Inhibition J. Biol. Chem., July 4, 2008; 283(27): 18601 - 18611. [Abstract] [Full Text] [PDF] P. Baumgartner, M. Geiger, S. Zieseniss, J. Malleier, J. A. Huntington, K. Hochrainer, E. Bielek, M. Stoeckelhuber, K. Lauber, D. Scherfeld, et al. Phosphatidylethanolamine critically supports internalization of cell-penetrating protein C inhibitor J. Cell Biol., November 19, 2007; 179(4): 793 - 804. [Abstract] [Full Text] [PDF]

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