The novel inhibitory receptor G6B is expressed on the surface of platelets and attenuates platelet function in vitro

Author:

Newland Stephen A.1,Macaulay Iain C.2,Floto Andres R.1,de Vet Edwin C.3,Ouwehand Willem H.2,Watkins Nicholas A.2,Lyons Paul A.1,Campbell Duncan R.4

Affiliation:

1. Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom;

2. National Blood Service Cambridge and Department of Haematology, University of Cambridge, Cambridge, United Kingdom;

3. MRC Rosalind Franklin Centre for Genomics Research, Hinxton, Cambridge, United Kingdom;

4. Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom

Abstract

Abstract The G6B cell-surface receptor, which contains a single Ig-like domain, has been shown to bind to SHP-1 and SHP-2 after phosphorylation of 2 immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in its cytoplasmic tail, classifying this protein as a new member of the family of inhibitory receptors. In this study, we demonstrate by real-time polymerase chain reaction (PCR) and Western-blot analysis that G6B is expressed on platelets. Cross-linking of G6B with polyclonal antisera has a significant inhibitory effect on platelet aggregation and activation by agonists such as ADP and collagen-related peptide (CRP). This inhibitory function of G6B appears to operate in a calcium-independent manner. Our results suggest that G6B represents a novel inhibitory receptor found on the surface of platelets and that it could be an antithrombotic drug target.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Reference13 articles.

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2. G6b, a novel immunoglobulin superfamily member encoded in the human major histocompatibility complex, interacts with SHP-1 and SHP-2.;de Vet;J Biol Chem,2001

3. Inhibitory receptors, ITIM sequences and phosphatases.;Unkeless;Curr Opin Immunol,1997

4. The cell surface receptor G6b, a member of the immunoglobulin superfamily, binds heparin.;de Vet;FEBS Lett,2005

5. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.;Livak;Methods,2001

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