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Blood, 1 March 2005, Vol. 105, No. 5, pp. 1986-1991. Prepublished online as a Blood First Edition Paper on October 28, 2004; DOI 10.1182/blood-2004-04-1365. This Article Full Text (PDF) All Versions of this Article: 2004-04-1365v1 105/5/1986    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 Cruz, M. A Articles by Lopez, J. A Search for Related Content PubMed PubMed Citation Articles by Cruz, M. A Articles by Lopez, J. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 13, 2004 Accepted October 26, 2004 The platelet glycoprotein Ib - von Willebrand Factor interaction activates the collagen receptor 21 to bind collagen: activation-dependent conformational change of the 2-I domain Miguel A Cruz*, Junmei Chen, Jody L Whitelock, Liza D Morales, and Jose A Lopez Thrombosis Research Section, Department of Medicine, Baylor College of Medicine, Houston, TX, USA * Corresponding author; email: miguelc{at}bcm.tmc.edu. Integrin 21 (GP Ia/IIa) is a major platelet receptor for collagen, its principal collagen-binding site residing within the 2 I domain. 21 changes conformation upon platelet activation, increasing its affinity for collagen. We investigated whether this conformational change can be detected by monoclonal antibodies by comparing the binding of three antibodies to unstimulated or ADP-activated platelets. Two antibodies known to bind within the 2 I domain, 12F1 and 6F1, bound preferentially to ADP-activated platelets. Interestingly, when whole blood was perfused over a surface coated with either 12F1 or 6F1, only 6F1 supported the adhesion of unstimulated platelets. To test whether the interaction of GP Ib with VWF directly activates 21, we used 12F1 as a probe of integrin activation. We perfused blood over a surface coated with a mixture of VWF A1 domain (a GP Ib ligand) and 12F1 or VWF A1 and mouse IgG. Platelets rolled and did not attach stably on the A1/IgG surface, but they firmly bound and covered the A1/12F1 surface. We corroborated that 12F1 binds an active conformation of the I domain by showing that it binds with higher affinity to a gain-of-function mutant than to either wild-type I domain or a loss-of-function mutant. These results strongly suggest that the interaction of platelet GP Ib with VWF mediates the activation of 21, increasing its affinity for collagen. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. J. Lambert, A. A. Bobkov, J. W. Smith, and F. M. Marassi Competitive Interactions of Collagen and a Jararhagin-derived Disintegrin Peptide with the Integrin {alpha}2-I Domain J. Biol. Chem., June 13, 2008; 283(24): 16665 - 16672. [Abstract] [Full Text] [PDF] C. N. Morrell, K. Murata, A. M. Swaim, E. Mason, T. V. Martin, L. E. Thompson, M. Ballard, K. Fox-Talbot, B. Wasowska, and W. M. Baldwin III In Vivo Platelet-Endothelial Cell Interactions in Response to Major Histocompatibility Complex Alloantibody Circ. Res., April 11, 2008; 102(7): 777 - 785. [Abstract] [Full Text] [PDF] A. Kauskot, F. Adam, A. Mazharian, N. Ajzenberg, E. Berrou, A. Bonnefoy, J.-P. Rosa, M. F. Hoylaerts, and M. Bryckaert Involvement of the Mitogen-activated Protein Kinase c-Jun NH2-terminal Kinase 1 in Thrombus Formation J. Biol. Chem., November 2, 2007; 282(44): 31990 - 31999. 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