Signaling through G Proteins and G Protein-coupled Receptors during Platelet Activation

Lawrence F Brass; James A Hoxie; David R Manning

doi:10.1055/s-0038-1646194

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1993; 70(01): 217-223
DOI: 10.1055/s-0038-1646194

State-of-the-Art Lecture

Platelet Signaling

Schattauer GmbH Stuttgart

Signaling through G Proteins and G Protein-coupled Receptors during Platelet Activation

Lawrence F Brass

Departments of Medicine, Pathology and Pharmacology, University of Pennsylvania. Philadelphia, PA, USA

,

James A Hoxie

Departments of Medicine, Pathology and Pharmacology, University of Pennsylvania. Philadelphia, PA, USA

,

David R Manning

Departments of Medicine, Pathology and Pharmacology, University of Pennsylvania. Philadelphia, PA, USA

› Author Affiliations

Abstract

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Summary

Recent studies have helped to define the early events of signal transduction in platelets. The best-described of these events are those in which heterotrimeric guanine nucleotide binding regulatory proteins (G proteins) mediate the interaction between cell surface receptors for agonists and intracellular second messenger generating enzymes. To date nine different G proteins have been identified in platelets. The:r targets include phospholipases C and A₂, and adenylyl cyclase. Efforts to clone the receptors that can couple to these G proteins have been successful for epinephrine, thrombin, TxA₂ and platelet activating factor. Each of these is comprised of a single polypeptide with seven transmembrane domains and an extracellular N-terminus. In the case of the thrombin receptor, activation occurs by a novel mechanism in which thrombin cleaves its receptor, creating a new N-terminus that can serve as a tethered ligand. Shortly after activation, thrombin receptors become resistant to re-activation by thrombin. This desensitization, which appears to involve receptor phosphorylation and internalization, provides a potent mechanism for limiting the duration of thrombin-initiated events in platelets and other thrombin-responsive vascular cells.

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References

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