title: Characterization of a ligand-attenuated binding site on glycoprotein IIb/IIIa.
abstract: We describe an epitope on the platelet integrin, GPIIb/IIIa, identified by the monoclonal antibody, 4F8, which is attenuated by small-molecule GPIIb/IIIa ligands. 4F8 did not bind to the ligand binding pocket as it did not compete with a radiolabelled antagonist, (3)H-SC-52012. This indicates that the 4F8 epitope behaves as a ligand-attenuated binding site (LABS). Ligand-induced attenuation of 4F8 was an active process as it was prevented by pretreating platelets with cytochalasin D and reduced by prostaglandin E(1) or inhibition of protein kinase C. Disappearance of the epitope was required for full platelet activation as 4F8 prevented platelet aggregation without inhibiting fibrinogen binding. These results suggest a model where disappearance of the 4F8 epitope is a secondary event required for full "outside-in" signaling through GPIIb/IIIa.
authors.affiliation: Centre for Cardiovascular Science, The Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Quinn
authors.forename: John
authors.initials: J
authors.lastname: Fullard
authors.forename: Steven
authors.initials: S
authors.lastname: Kerrigan
authors.forename: Patrick
authors.initials: P
authors.lastname: Harriott
authors.forename: Dermot
authors.initials: D
authors.lastname: Cox
authors.forename: Desmond J
authors.initials: DJ
authors.lastname: Fitzgerald
mesh_terms: D000527:Alprostadil / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001665:Binding Sites / Q000276:immunology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D015638:Cytochalasin D / Q000494:pharmacology; D000939:Epitopes; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008024:Ligands; D015539:Platelet Activation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism* / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D015398:Signal Transduction
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D008024:Ligands; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D015638:Cytochalasin D; D005340:Fibrinogen; D011493:Protein Kinase C; D000527:Alprostadil