The novel inhibitory receptor G6B is expressed on the surface of platelets and attenuates platelet function in vitro.
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.
Newland
Stephen A
SA
Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Addembrookes Hospital, Hills Road, Cambridge, UK.
Macaulay
Iain C
IC
Floto
Andres R
AR
de Vet
Edwin C
EC
Ouwehand
Willem H
WH
Watkins
Nicholas A
NA
Lyons
Paul A
PA
Campbell
Duncan R
DR
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
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