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Thromb Haemost 2002; 88(05): 811-816
DOI: 10.1055/s-0037-1613307
Review Article
Schattauer GmbH

Characterization of a Ligand-attenuated Binding Site on Glycoprotein IIb/IIIa

Martin J. Quinn
1   Centre for Cardiovascular Science, The Royal College of Surgeons in Ireland, Dublin, Ireland
,
John Fullard
1   Centre for Cardiovascular Science, The Royal College of Surgeons in Ireland, Dublin, Ireland
,
Steven Kerrigan
1   Centre for Cardiovascular Science, The Royal College of Surgeons in Ireland, Dublin, Ireland
,
Patrick Harriott
2   Centre for Peptide and Protein Engineering, Queen’s University Belfast, Northern Ireland
,
Dermot Cox
1   Centre for Cardiovascular Science, The Royal College of Surgeons in Ireland, Dublin, Ireland
,
Desmond J. Fitzgerald
1   Centre for Cardiovascular Science, The Royal College of Surgeons in Ireland, Dublin, Ireland
› Author Affiliations
Further Information

Publication History

Received 25 October 2001

Accepted after resubmission 24 July 2002

Publication Date:
08 December 2017 (online)

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Summary

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, 3H-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 E1 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.

Keywords

Integrin - glycoprotein IIb/IIIa - conformational change - platelet - thrombosis
 

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