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14 - Platelet signalling: GTP-binding proteins

from PART I - PHYSIOLOGY

Published online by Cambridge University Press:  10 May 2010

Jan-Willem N. Akkerman
Affiliation:
Laboratory for Thrombosis and Haemostasis, Department of Haematology, University Medical Center Utrecht, The Netherlands
Paolo Gresele
Affiliation:
Università degli Studi di Perugia, Italy
Clive P. Page
Affiliation:
Sackler Institute of Pulmonary Pharmacology and Therapeutics, Guy's, King's and St Thomas' School of Biomedical Sciences, London
Valentin Fuster
Affiliation:
Mount Sinai Medical Center and School of Medicine, New York
Jos Vermylen
Affiliation:
Universiteitsbibliotheek-K.U., Leuven
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Summary

Introduction

To respond to extracellular signals, platelets possess different types of surface receptors for stimulatory and inhibitory ligands. Surface receptors can be classified in three groups each possessing a specific property by which information is relayed through the plasma membrane. These are: (i) G-protein linked receptors, (ii) enzyme linked receptors and, (iii) ion channel-linked receptors. G-protein linked receptors are seven transmembrane receptors that relay the stimulus to high molecular weight, heterotrimeric GTP-binding regulatory proteins (G-proteins in short) consisting of three polypeptides, an α-, a β- and a γ- subunit. Enzyme linked receptors have a single transmembrane domain and contain a cytosolic tail with an intrinsic enzyme activity or that associates directly with an enzyme. They start signalling cascades that involve a second class of GTP-binding proteins which are low molecular weight, monomeric GTPases (small GTPases in short). Ion channel linked receptors respond directly to ligand binding by opening a channel pore resulting in single channel currents.

Both G-proteins and small GTPases are members of the superfamily of GTPases. They function as molecular switches between a GTP-bound ‘on-state’ and a GDPbound ‘off-state’. Hence, they are important elements in the initiation and termination of signal transduction. In addition, they serve in amplification of signals helping to convert a weak extracellular stimulus into a strong intracellular signal. The fact that one G-protein might be connected to several receptors or couple to more than one downstream effector enables integration of different signals. Thus, GTP-binding proteins are key elements in the signalling cascades that initiate shape change, aggregation, secretion and contraction, or prevent this.

Type
Chapter
Information
Platelets in Thrombotic and Non-Thrombotic Disorders
Pathophysiology, Pharmacology and Therapeutics
, pp. 204 - 220
Publisher: Cambridge University Press
Print publication year: 2002

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