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14 - Platelet signalling: GTP-binding proteins
- from PART I - PHYSIOLOGY
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- By Jan-Willem N. Akkerman, Laboratory for Thrombosis and Haemostasis, Department of Haematology, University Medical Center Utrecht, The Netherlands
- Edited by Paolo Gresele, Università degli Studi di Perugia, Italy, Clive P. Page, Valentin Fuster, Jos Vermylen, Universiteitsbibliotheek-K.U., Leuven
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- Book:
- Platelets in Thrombotic and Non-Thrombotic Disorders
- Published online:
- 10 May 2010
- Print publication:
- 30 May 2002, pp 204-220
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- Chapter
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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.