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Prepublished online as a Blood First Edition Paper on October 10, 2002; DOI 10.1182/blood-2002-08-2353. This Article Full Text (PDF) All Versions of this Article: 2002-08-2353v1 101/4/1416    most recent Alert me when this article is cited Alert me if a correction is posted 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 Mille-Baker, B. Articles by Laffan, M. A Search for Related Content PubMed PubMed Citation Articles by Mille-Baker, B. Articles by Laffan, M. A Social Bookmarking                   What's this? Submitted August 1, 2002 Accepted September 19, 2002 Deletion or replacement of the second EGF-like domain of protein S results in loss of APC cofactor activity Blandine Mille-Baker, Suely M Rezende, Rachel E Simmonds, David A Lane, and Michael A Laffan* Department of Haematology, Imperial College, Hammersmith Hospital, London, United Kingdom * Corresponding author; email: m.laffan{at}ic.ac.uk. Human protein S (PS), a cofactor of anticoagulant activated protein C (APC), is a modular protein containing four EGF-like domains. EGF1 appears to mediate PS interaction with APC but the roles of EGF's 2,3&4 are less clear. We synthesized PS variants lacking single EGF domains (EGF2, 3 or 4) and assessed their APC cofactor activity in a factor Va inactivation assay. The variant lacking EGF2 (variant 134) showed the most dramatic loss of activity (~10% of recombinant wild type PS (wtPS) activity). Replacement of EGF2 by an additional EGF3 (variant 1334) resulted in a comparable loss of activity, suggesting that the loss of a specific rather than a 'spacer' function of EGF2 was responsible. We confirmed that the variant 134 had a functional Gla-domain and that EGF1 was correctly folded. This is the first clear evidence that EGF2 is required for the expression of PS activity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Harmon, R. J. S. Preston, F. N. Ainle, J. A. Johnson, M. S. Cunningham, O. P. Smith, B. White, and J. S. O'Donnell Dissociation of Activated Protein C Functions by Elimination of Protein S Cofactor Enhancement J. Biol. Chem., November 7, 2008; 283(45): 30531 - 30539. [Abstract] [Full Text] [PDF] S.-Y. Park, S.-Y. Kim, M.-Y. Jung, D.-J. Bae, and I.-S. Kim Epidermal Growth Factor-Like Domain Repeat of Stabilin-2 Recognizes Phosphatidylserine during Cell Corpse Clearance Mol. Cell. Biol., September 1, 2008; 28(17): 5288 - 5298. [Abstract] [Full Text] [PDF] R. J. S. Preston, E. Ajzner, C. Razzari, S. Karageorgi, S. Dua, B. Dahlback, and D. A. Lane Multifunctional Specificity of the Protein C/Activated Protein C Gla Domain J. Biol. Chem., September 29, 2006; 281(39): 28850 - 28857. [Abstract] [Full Text] [PDF] F. Saller, B. O. Villoutreix, A. Amelot, T. Kaabache, B. F. Le Bonniec, M. Aiach, S. Gandrille, and D. Borgel The {gamma}-carboxyglutamic acid domain of anticoagulant protein S is involved in activated protein C cofactor activity, independently of phospholipid binding Blood, January 1, 2005; 105(1): 122 - 130. [Abstract] [Full Text] [PDF] S. M. Rezende, R. E. Simmonds, and D. A. Lane Coagulation, inflammation, and apoptosis: different roles for protein S and the protein S-C4b binding protein complex Blood, February 15, 2004; 103(4): 1192 - 1201. [Abstract] [Full Text] [PDF]

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