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Blood, 1 November 2005, Vol. 106, No. 9, pp. 3028-3034. Prepublished online as a Blood First Edition Paper on July 21, 2005; DOI 10.1182/blood-2005-01-0333. This Article Full Text (PDF) All Versions of this Article: 2005-01-0333v1 106/9/3028    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 Nanda, N. Articles by Phillips, D. R Search for Related Content PubMed PubMed Citation Articles by Nanda, N. Articles by Phillips, D. R Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 25, 2005 Accepted June 10, 2005 Platelet aggregation induces platelet aggregate stability via SLAM family receptor signaling Nisha Nanda, Patrick Andre, Ming Bao, Karl Clauser, Francis Deguzman, Duncan Howie, Pamela B Conley, Cox Terhorst, and David R Phillips* Portola Pharmaceuticals Inc., San Francisco, CA, USA; Millennium Pharmaceuticals Inc., San Francisco, CA, USA Millennium Pharmaceuticals Inc., San Francisco, CA, USA Millennium Pharmaceuticals Inc., Cambridge, MA, USA Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA * Corresponding author; email: dphillips{at}portola.com. Platelet aggregation is a dynamic entity, capable of directing its own growth and stability via the activation of signaling cascades that lead to the expression and secretion of various secondary agonists. Here we show that the signaling pathways triggered during platelet aggregation include an intrinsic pro-thrombotic activity mediated by two homophilic adhesion molecules, CD84 and CD150 (SLAM), which are tyrosine phosphorylated in a platelet aggregation-dependent fashion. The two CD84/SLAM adapter proteins, SAP (SLAM-associated protein) and EAT-2 (EWS-activated transcript-2) were both found in platelets; only SAP however, was found to immunoprecipitate with tyrosine phosphorylated SLAM. The immobilized extracellular domain of CD84 promoted microaggregate formation while SAP-deficient platelets demonstrated defective spreading on immobilized CD84 demonstrating a functional role in platelets for SLAM family interactions. Finally, analysis of SLAM-deficient mice revealed an overall defect in platelet aggregation in vitro, and a delayed arterial thrombotic process in vivo. The data indicate that signaling of the adhesion molecules in the SLAM family, activated by proximity during aggregation further stabilize platelet-platelet interactions in thrombosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The SLAM family of receptors: new players in platelet aggregation José A.López Blood 2005 106: 2929-2930. [Full Text] [PDF] This article has been cited by other articles: J. M. Auger and S. P. Watson Dynamic Tyrosine Kinase-Regulated Signaling and Actin Polymerisation Mediate Aggregate Stability Under Shear Arterioscler. Thromb. Vasc. Biol., August 1, 2008; 28(8): 1499 - 1504. [Abstract] [Full Text] [PDF] L. F. Brass, L. Zhu, and T. J. Stalker Novel Therapeutic Targets at the Platelet Vascular Interface Arterioscler. Thromb. Vasc. 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Tomlinson, A. Garcia, S. Dumon, V. L. Heath, J. Herbert, S. P. Cobbold, J. C. Spalton, S. Ayman, R. Antrobus, et al. A Comprehensive Proteomics and Genomics Analysis Reveals Novel Transmembrane Proteins in Human Platelets and Mouse Megakaryocytes Including G6b-B, a Novel Immunoreceptor Tyrosine-based Inhibitory Motif Protein Mol. Cell. Proteomics, March 1, 2007; 6(3): 548 - 564. [Abstract] [Full Text] [PDF] S. Ohno, N. Ono, F. Seki, M. Takeda, S. Kura, T. Tsuzuki, and Y. Yanagi Measles Virus Infection of SLAM (CD150) Knockin Mice Reproduces Tropism and Immunosuppression in Human Infection J. Virol., February 15, 2007; 81(4): 1650 - 1659. [Abstract] [Full Text] [PDF] J. M. E. M. Cosemans, I. C. A. Munnix, R. Wetzker, R. Heller, S. P. Jackson, and J. W. M. Heemskerk Continuous signaling via PI3K isoforms beta and {gamma} is required for platelet ADP receptor function in dynamic thrombus stabilization Blood, November 1, 2006; 108(9): 3045 - 3052. [Abstract] [Full Text] [PDF] P. Eissmann and C. Watzl Molecular Analysis of NTB-A Signaling: A Role for EAT-2 in NTB-A-Mediated Activation of Human NK Cells. J. Immunol., September 1, 2006; 177(5): 3170 - 3177. [Abstract] [Full Text] [PDF] R. Bhat, P. Eissmann, J. Endt, S. Hoffmann, and C. Watzl Fine-tuning of immune responses by SLAM-related receptors J. Leukoc. Biol., March 1, 2006; 79(3): 417 - 424. [Abstract] [Full Text] [PDF]

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