title: The novel inhibitory receptor G6B is expressed on the surface of platelets and attenuates platelet function in vitro.
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.
authors.affiliation: Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Addembrookes Hospital, Hills Road, Cambridge, UK.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Newland
authors.forename: Iain C
authors.initials: IC
authors.lastname: Macaulay
authors.forename: Andres R
authors.initials: AR
authors.lastname: Floto
authors.forename: Edwin C
authors.initials: EC
authors.lastname: de Vet
authors.forename: Willem H
authors.initials: WH
authors.lastname: Ouwehand
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Watkins
authors.forename: Paul A
authors.initials: PA
authors.lastname: Lyons
authors.forename: Duncan R
authors.initials: DR
authors.lastname: Campbell
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry; D001792:Blood Platelets / Q000378:metabolism*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002352:Carrier Proteins; D003432:Cross-Linking Reagents; C119883:MPIG6B protein, human; D008565:Membrane Proteins; D010455:Peptides; D020033:Protein Isoforms; D011971:Receptors, Immunologic; C435908:collagen-related peptide; D000244:Adenosine Diphosphate