The present study was designed to examine the interaction of the purified platelet glycoprotein IIb-IIIa complex (GP IIb-IIIa or integrin alpha IIb beta 3) and the individual subunits of the complex with immobilized fibrinogen. Although 125I-GP IIb-IIIa binding to fibrinogen immobilized on Sepharose was specific, this interaction exhibited properties distinct from those of reversible fibrinogen binding to platelets: 125I-GP IIb-IIIa binding appeared irreversible, but non-covalent, Ca(2+)-independent, and was inhibited only weakly, or not at all, by the anti-(GP IIb-IIIa) monoclonal antibodies 10E5 and 7E3 and synthetic peptides from known platelet-binding domains of fibrinogen. Reversibly dissociated GP IIb or GP IIIa subunits inhibited 125I-GP IIb-IIIa binding to immobilized fibrinogen and bound directly to the fibrinogen. However, these subunits did not bind to peptides derived from known platelet-binding domains within the fibrinogen alpha- and gamma-chains, although the GP IIb-IIIa complex did. These results show that the complexed form of full-length GP IIb and GP IIIa is required for binding to these synthetic peptides, but not necessarily for binding to immobilized fibrinogen. Thus GP IIb-IIIa can bind to immobilized fibrinogen by a distinct mechanism that appears to involve novel binding sites on each subunit of the GP IIb-IIIa complex and on fibrinogen.
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Research Article|
January 15 1993
Evidence for novel binding sites on the platelet glycoprotein IIb and IIIa subunits and immobilized fibrinogen
L V Parise
;
L V Parise
*
Gladstone Institute of Cardiovascular Disease, Cardiovascular Research Institute, University of California, San Francisco 94141-9100, U.S.A.
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B Steiner
;
B Steiner
*
Gladstone Institute of Cardiovascular Disease, Cardiovascular Research Institute, University of California, San Francisco 94141-9100, U.S.A.
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L Nannizzi
;
L Nannizzi
*
Gladstone Institute of Cardiovascular Disease, Cardiovascular Research Institute, University of California, San Francisco 94141-9100, U.S.A.
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A B Criss
;
A B Criss
†
Department of Pharmacology and Center for Thrombosis and Hemostasis, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7365, U.S.A.
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D R Phillips
D R Phillips
*
Gladstone Institute of Cardiovascular Disease, Cardiovascular Research Institute, University of California, San Francisco 94141-9100, U.S.A.¶
Department of Pathology, University of California, San Francisco, CA 94141-9100, U.S.A.
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Biochem J (1993) 289 (2): 445-451.
Citation
L V Parise, B Steiner, L Nannizzi, A B Criss, D R Phillips; Evidence for novel binding sites on the platelet glycoprotein IIb and IIIa subunits and immobilized fibrinogen. Biochem J 15 January 1993; 289 (2): 445–451. doi: https://doi.org/10.1042/bj2890445
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