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This Article Full Text Full Text (PDF) Retraction (v110,p4164) 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 Sun, M.-F. Articles by Gailani, D. Search for Related Content PubMed PubMed Citation Articles by Sun, M.-F. Articles by Gailani, D. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 July 2001, Vol. 98, No. 1, pp. 125-129 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Defective binding of factor XI-N248 to activated human platelets Mao-Fu Sun, Frank A. Baglia, David Ho, Danko Martincic, Russell E. Ware, Peter N. Walsh, and David Gailani From the Departments of Pathology and Medicine, Vanderbilt University, Nashville, TN; the Sol Sherry Thrombosis Research Center, Departments of Medicine and Biochemistry, Temple University School of Medicine, Philadelphia, PA; and the Department of Pediatrics, Duke University Medical Center, Durham, NC. Variants of factor XI containing Gln226 to Arg (Q226 to R) and Ser248 to Asn (S248 to N) substitutions were first identified in an African American family with a history of excessive bleeding. The substitutions have recently been identified in unrelated individuals, suggesting they are relatively common. Both amino acids are located in the third apple domain of factor XI, an area implicated in binding interactions with factor IX and activated platelets. Recombinant factor XI-R226 and factor XI-N248 were compared with wild-type factor XI in assays for factor IX activation or platelet binding. Factor XI-R226 activates factor IX with a Michaelis-Menten constant (Km) about 5-fold greater than wild-type protein. The catalytic efficiency of factor IX activation is similar to wild-type protein, however, due to an increase in the turnover number (kcat) for the reaction. Iodinated factor XI-N248 binds to activated platelets with a dissociation constant (Kd) more than 5-fold higher than wild-type protein (55 nM and 10 nM, respectively). Activation of factor XI-N248 by thrombin in the presence of activated platelets is slower and does not progress to the same extent as activation of the wild-type protein under similar conditions. Factor XI-N248 activates factor IX normally in a purified protein system and has relatively normal activity in activated partial thromboplastin time (aPTT) assays. Factor XI-N248 is the first factor XI variant described with a clear functional difference compared with wild-type protein. Importantly, the defect in platelet binding would not be detected by routine clinical evaluation with an aPTT assay. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. A. Baglia, D. Gailani, J. A. Lopez, and P. N. Walsh Identification of a Binding Site for Glycoprotein Ib{alpha} in the Apple 3 Domain of Factor XI J. Biol. Chem., October 29, 2004; 279(44): 45470 - 45476. [Abstract] [Full Text] [PDF]

	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020