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Regulation of Platelet Adhesion Receptors

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Platelets in Thrombotic and Non-Thrombotic Disorders

Abstract

Platelet adhesion to subendothelial matrices and cohesion to other platelets is essential for hemostasis, but recent studies have revealed that platelet adhesive interactions may also generate cross-talk with other cell types, including leukocytes, tumor cells, and microbial pathogens. In so doing, these adhesive interactions may impact a variety of protective or disease-promoting processes, and they are mediated by platelet adhesion receptors from several gene families, most notably integrins, as exemplified by the platelet-restricted integrin, αIIbβ3. During hemostasis, multiple brakes and controls on platelet adhesion receptors prevent pathological thrombosis. Thus, threshold levels of excitatory stimuli must be surpassed and sufficient to drive intracellular signaling for full activation of integrin receptors. Stimuli for primary hemostasis derive from released or generated soluble agonists, vascular matrices exposed by vessel injury, or by hydrodynamic shear stress. While the non-integrin adhesion receptor, GPIb-V-IX, is critical for platelet adhesion to matrix von Willebrand factor (VWF) during hemostasis and is a mediator of platelet aggregation through interactions with VWF at pathologically high shear stresses in atherosclerotic arteries, finely regulated interactions of αIIbβ3 with fibrinogen and other Arg-Gly-Asp (RGD)-containing ligands are required for platelet aggregation in hemostatic thrombi. In this chapter we present an overview of classical and nonclassical regulation of platelet adhesion receptors and associated signaling pathways, with a principle focus on platelet signaling pathways that converge on and regulate αIIbβ3.

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  1. Hematology-Oncology Division, Department of Medicine, University of California San Diego, Leichtag Biomedical Research Building, 9500 Gilman Drive, La Jolla, CA, 92093-0726, USA

    Ana Kasirer-Friede & Sanford J. Shattil

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  1. Ana Kasirer-Friede
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  2. Sanford J. Shattil
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Correspondence to Ana Kasirer-Friede .

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  1. Department of Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia , Perugia, Italy

    Paolo Gresele

  2. Houston Methodist Hospital , Houston, Texas, USA

    Neal S. Kleiman

  3. Bloodworks Northwest, University of Washington , Seattle, Washington, USA

    José A. Lopez

  4. Sackler Inst of Pulmonary Pharmacol, King’s College London, London, United Kingdom

    Clive P. Page

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Kasirer-Friede, A., Shattil, S.J. (2017). Regulation of Platelet Adhesion Receptors. In: Gresele, P., Kleiman, N., Lopez, J., Page, C. (eds) Platelets in Thrombotic and Non-Thrombotic Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-47462-5_6

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