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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:285.)
© 2000 American Heart Association, Inc.

Brief Reviews

Congenital Disorders of Platelet Signal Transduction

A. Koneti Rao; Jagadeesh Gabbeta

From the Department of Medicine and the Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pa.

Key Words: congenital platelet function disorders • signal transduction defects • disorders of secretion

	Introduction

 
After injury to the blood vessel, platelets adhere to the exposed subendothelium by a process (adhesion) that involves the interaction of a plasma protein, von Willebrand factor (vWF), and a specific protein on the platelet surface, glycoprotein Ib (GPIb; the Figure). Adhesion is followed by recruitment of additional platelets that form clumps, a process called aggregation (cohesion). This involves binding of fibrinogen to specific platelet surface receptors—a complex comprising glycoproteins IIb-IIIa (GPIIb-IIIa). Activated platelets release the contents of their granules (secretion or release reaction), such as ADP and serotonin from dense granules, which subsequently cause recruitment of additional platelets. In addition, platelets play a major role in coagulation mechanisms; several key enzymatic reactions occur on the platelet membrane–lipoprotein surface. A number of physiological agonists interact with specific receptors on the platelet surface to induce responses, including a change in platelet shape from discoid to spherical, aggregation, secretion, and thromboxane A₂ (TxA₂) production. Other agonists such as prostacyclin inhibit these responses. Ligation of the platelet receptors initiates the production or release of several intracellular messenger molecules, including Ca²⁺ ions, products of phosphoinositide (PI) hydrolysis by phospholipase C (PLC; diacylglycerol [DG] and inositol 1,4,5-triphosphate [InsP₃]), TxA₂, and cyclic nucleotides (cAMP; the Figure). These subsequently induce or modulate the various platelet responses of Ca²⁺ mobilization, protein phosphorylation, aggregation, secretion, and liberation of arachidonic acid. The interaction between the agonist receptors and the key intracellular effector enzymes (eg, PLA₂, PLC, adenylyl cyclase) is mediated by a group of . . . [Full Text of this Article]

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