The Platelet

✍ Scribed by E. Edward Bittar and Eduardo G. Lapetina (Eds.)

• Publisher: Elsevier Science
• Year: 1997
• Tongue: English
• Leaves: 394
• Series: Advances in Molecular and Cell Biology 18
• Edition: 1
• Category: Library

✦ Synopsis

Platelets have been an important model system in which to study various aspects of signal transduction. In spite of the fact that platelets are anucleated cells, it has been possible to assess the relationship between receptors, transducers and effectors, and specific platelet physiological responses. As a consequence, discrete biochemical events can be related to shape change, aggregation, and secretion. In addition to undergoing these internal biochemical changes, activated platelets express glycoproteins receptors for adhesive proteins on their surfaces; these help consolidation of the initial platelet aggregate to stop bleeding and start repair. When this protective action of platelets is exaggerated, a pathological situation arises. Abnormal platelet function is associated with thrombosis, atherosclerosis, and bleeding disorders.
This book deals with the most important aspects of platelet signal transduction that have been revealed in the past few years. Emphasis is given to knowledge gained in the area of glycoprotein receptors or integrins that bind adhesive proteins and play a crucial role in thrombosis. One of these integrins also serves as a collagen receptor on platelets. Collagen and thrombin are primary activators at sites of vascular injury. The main thrombin receptor recently was recognized as a seven trans-membrane domain receptor, and attention is now focused on the development of thrombin receptor antagonists that might prove to be useful in treatment of thrombosis and restenosis. The formation and release of thromboxane A2 n activated platelets help to recruit additional platelets to the injury site; the receptor for thromboxane A2 is a newly discovered seven trans-membrane domain receptor that is also covered in this book.
The coupling of platelet receptors to the effectors or second-messenger-producting enzymes is mostly through heterotrimeric and low molecular weight GTP-binding proteins, which have an important role in the stimulation or inhibition of platelet effectors. Two chapters deal with the role of GTP-binding proteins in human platelets. Several chapters are devoted to the effectors, including phospholipases C, A2, D, and phosphatidylinositol 3-kinase; the mobilization of Ca²⁺; and the formation of cAMP, cGMP, nitric oxide, and the role of the NA⁺/K⁺ exchanger. This is integrated with information on the activation of important protein kinases - that is, protein kinase C, Ca²⁺ -calmodulin-dependent protein kinases, cAMP and cGMP-dependent kinases, and tyrosine kinases - and on how these activities lead to changes in platelet cytoskeleton to cause shape change, aggregation, and secretion.

✦ Table of Contents

Content:
Edited by
Page iii

Copyright page
Page iv

List of Contributors
Pages vii-ix

Preface
Pages xi-xii
Eduardo G. Lapetina

Platelet Morphology, Aggregation, and Secretion Original Research Article
Pages 1-29
Archibald McNicol, Jon M. Gerrard

Platelet Adhesion Receptors Original Research Article
Pages 31-66
Kenneth J. Clemetson

The Platelet Integrin, GP IIb-IIIa (α_IIbß₃) Original Research Article
Pages 67-108
Charles Abrams, Sanford J. Shattil

The α₂ß₁ Integrin: Structure, Function, and Regulation of a Platelet Surface Collagen Receptor Original Research Article
Pages 109-128
Samuel A. Santoro, Edwin U.M. Saelman, Mary M. Zutter

The Platelet Thrombin Receptor Original Research Article
Pages 129-143
Shaun R. Coughlin

Platelet Arachidonic Acid Metabolism and Eicosanoid Receptors Original Research Article
Pages 145-177
Claire J. Allan, Perry V. Halushka

G Proteins and the Early Events of Platelet Activation Original Research Article
Pages 179-195
Lawrence F. Brass, Mortimer Poncz, David R. Manning

The Role of Low Molecular Weight GTP-Binding Proteins in Human Platelets Original Research Article
Pages 197-251
Mauro Torti, Eduardo G. Lapetina

The Role of Signal-Transducing Phospholipases A₂2, C, and D in Platelet Activation Original Research Article
Pages 253-274
Shigeru Nakashima, Yoshiko Banno, Yoshinori Nozawa

Ca²⁺ and Protein Kinase C in Platelets Original Research Article
Pages 275-310
James D. Chang, J. Anthony Ware

Signal Transduction by Cyclic Nucleotide-Dependent Protein Kinases in Platelets Original Research Article
Pages 311-333
Elke Butt, Ulrich Walter

Protein Tyrosine Phosphorylation in Platelets Original Research Article
Pages 335-352
Joan S. Brugge, Edwin A. Clark, Sanford J. Shattil

Na⁺/H⁺ Exchange in Platelets Original Research Article
Pages 353-366
Rienk Nieuwland, Jan-WillemNicolaas Akkerman

Regulation of Platelet Function by Nitric Oxide Original Research Article
Pages 367-381
Marek W. Radomski, Salvador Moncada

Index
Pages 383-394