Date Published: November 24, 2009
Publisher: Public Library of Science
Author(s): Karen E. Drahos, John D. Welsh, Carla V. Finkielstein, Daniel G. S. Capelluto, Bostjan Kobe. http://doi.org/10.1371/journal.pone.0008007
Abstract: Platelets contact each other at the site of vascular injury to stop bleeding. One negative regulator of platelet aggregation is Disabled-2 (Dab2), which is released to the extracellular surface upon platelet activation. Dab2 inhibits platelet aggregation through its phosphotyrosine-binding (PTB) domain by competing with fibrinogen for αIIbβ3 integrin receptor binding by an unknown mechanism.
Partial Text: Platelets are anucleate cell fragments that contact each other to form a plug at the site of vascular injury. Platelets contain both α- and δ-granules that contribute to their adhesion, activation, and aggregation . Granules contain a variety of proteins including adhesive and plasma proteins, coagulation and anti-coagulation factors, and protease inhibitors . Platelet adhesion to a prothrombotic surface is mediated by the formation of the glycoprotein Ib-IX-V and von Willebrand factor (vWF) complex, which is followed by the release of granules and the activation of members of the integrin family of receptors. Activated platelets accelerate the coagulation process by providing the membrane surface necessary for the generation of the active form of thrombin, which acts as a potent platelet agonist (for review, see ). Thus, vWF initiates the formation of stable aggregates under high shear flow conditions. Other complexes, such as P-selectin-sulfatides and αIIbβ3 integrin-fibrinogen, also stabilize platelet aggregates. Thrombin cleaves fibrinogen to fibrin, which crosslinks platelets to form the haemostatic plug.