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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.
 Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
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
From Portola Pharmaceuticals and Millennium Pharmaceuticals, San Francisco, CA; the Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; and Millennium Pharmaceuticals, Cambridge, MA.
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 2 homophilic adhesion molecules, CD84 and CD150 (SLAM [signaling lymphocyte activation molecule]), which are tyrosine phosphorylated in a platelet aggregation–dependent fashion. The 2 CD84/SLAM adapter proteins, SAP (SLAM-associated protein) and EAT-2 (EWS-activated transcript-2), were 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.
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