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Blood, 15 September 2005, Vol. 106, No. 6, pp. 1982-1987. Prepublished online as a Blood First Edition Paper on June 2, 2005; DOI 10.1182/blood-2005-02-0514. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-02-0514v1 106/6/1982    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 Peng, Y. Articles by López, J. A. Search for Related Content PubMed PubMed Citation Articles by Peng, Y. Articles by López, J. A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Gain of von Willebrand factor–binding function by mutagenesis of a species-conserved residue within the leucine-rich repeat region of platelet glycoprotein Ib Yuandong Peng, Corie N. Shrimpton, Jing-fei Dong, and José A. López From the Thrombosis Research Section, Department of Medicine, Baylor College of Medicine, Houston, TX. Glycoprotein (GP) Ib, a member of the leucine-rich repeat (LRR) protein family, mediates platelet adhesion to immobilized von Willebrand factor (VWF). We investigated the role in VWF binding of charged residues in the LRR region of GP Ib that are conserved in human, canine, and murine proteins. Substitution of His86 with either Ala or Glu resulted in a gain of VWF-binding function as judged by increased VWF binding in the presence of the modulators ristocetin and botrocetin and by enhanced adhesion of Chinese hamster ovary (CHO) cells expressing the mutant GP Ib to immobilized VWF under conditions of flow. This is the first report of a gain-of-function phenotype resulting from mutations in the LRR region of GP Ib. Because His86 is 2 nm away from the region of GP Ib with the largest surface of contact with VWF, the data suggest that the LRRs regulate GP Ib affinity for VWF allosterically. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Vettore, R. Scandellari, S. Moro, A. M. Lombardi, M. Scapin, M. L. Randi, and F. Fabris Novel point mutation in a leucine-rich repeat of the GPIb{alpha} chain of the platelet von Willebrand factor receptor, GPIb/IX/V, resulting in an inherited dominant form of Bernard-Soulier syndrome affecting two unrelated families: the N41H variant Haematologica, November 1, 2008; 93(11): 1743 - 1747. [Abstract] [Full Text] [PDF] J. Lou, T. Yago, A. G. Klopocki, P. Mehta, W. Chen, V. I. Zarnitsyna, N. V. Bovin, C. Zhu, and R. P. McEver Flow-enhanced adhesion regulated by a selectin interdomain hinge J. Cell Biol., September 25, 2006; 174(7): 1107 - 1117. [Abstract] [Full Text] [PDF]

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