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Blood, 1 February 2007, Vol. 109, No. 3, pp. 1018-1025. Prepublished online as a Blood First Edition Paper on September 26, 2006; DOI 10.1182/blood-2006-05-022301. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-05-022301v1 109/3/1018    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 Kasirer-Friede, A. Articles by Shattil, S. J. Search for Related Content PubMed PubMed Citation Articles by Kasirer-Friede, A. Articles by Shattil, S. J. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY ADAP is required for normal IIbß3 activation by VWF/GP Ib-IX-V and other agonists Ana Kasirer-Friede1, Barry Moran1, Jennifer Nagrampa-Orje2, Ken Swanson3, Zaverio M. Ruggeri2, Burkhart Schraven4, Benjamin G. Neel3, Gary Koretzky5, and Sanford J. Shattil1 1 Department of Medicine, University of California San Diego, La Jolla; 2 Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA; 3 Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; 4 Institute of Immunology, University of Magdeburg, Germany; 5 Abramson Family Cancer Research Institute and Division of Rheumatology, University of Pennsylvania, Philadelphia Interaction between von Willebrand factor (VWF) and platelet GP Ib-IX-V is required for hemostasis, in part because intracellular signals from VWF/GP Ib-IX-V activate the ligand-binding function of integrin IIbß3. Because they also induce tyrosine phosphorylation of the ADAP adapter, we investigated ADAP's role in GP Ib-IX-V signal transduction. Fibrinogen or ligand-mimetic POW-2 Fab binding to IIbß3 was stimulated by adhesion of ADAP+/+ murine platelets to dimeric VWF A1A2 but was significantly reduced in ADAP–/– platelets (P < .01). IIbß3 activation by ADP or a Par4 thrombin receptor agonist was also decreased in ADAP–/– platelets. ADAP stabilized the expression of another adapter, SKAP-HOM, via interaction with the latter's SH3 domain. However, no abnormalities in IIbß3 activation were observed in SKAP-HOM–/– platelets, which express normal ADAP levels, further implicating ADAP as a modulator of IIbß3 function. Under shear flow conditions over a combined surface of VWF A1A2 and fibronectin to test interactions involving GP Ib-IX-V and IIbß3, respectively, ADAP–/– platelets displayed reduced IIbß3-dependent stable adhesion. Furthermore, ADAP–/– mice demonstrated increased rebleeding from tail wounds. These studies establish ADAP as a component of inside-out signaling pathways that couple GP Ib-IX-V and other platelet agonist receptors to IIbß3 activation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Prevost, J. V. Mitsios, H. Kato, J. E. Burke, E. A. Dennis, T. Shimizu, and S. J. Shattil Group IVA cytosolic phospholipase A2 (cPLA2{alpha}) and integrin {alpha}IIb{beta}3 reinforce each other's functions during {alpha}IIb{beta}3 signaling in platelets Blood, January 8, 2009; 113(2): 447 - 457. [Abstract] [Full Text] [PDF] M. Dittrich, I. Birschmann, S. Mietner, A. Sickmann, U. Walter, and T. Dandekar Platelet Protein Interactions: Map, Signaling Components, and Phosphorylation Groundstate Arterioscler. Thromb. Vasc. Biol., July 1, 2008; 28(7): 1326 - 1331. [Abstract] [Full Text] [PDF] D. Varga-Szabo, I. Pleines, and B. Nieswandt Cell Adhesion Mechanisms in Platelets Arterioscler. Thromb. Vasc. Biol., March 1, 2008; 28(3): 403 - 412. [Abstract] [Full Text] [PDF]

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