Identification of two distinct regions within the binding sites for fibrinogen and fibronectin on the IIb-IIIa human platelet membrane glycoprotein complex by monoclonal antibodies P2 and P4.
The effect of two monoclonal antibodies P2 (LyP 2) or P4 (LyP 4), specific for the platelet membrane glycoprotein IIb/IIIa complex, on binding of 125I-labelled fibrinogen or 125I-labelled fibronectin to thrombin-stimulated platelets was studied. These monoclonal antibodies are directed against different determinants on the IIb-IIIa complex and react only with the complex and not with the individual glycoproteins. Fibrinogen binding to thrombin-stimulated platelets was significantly inhibited by P2 but not by P4. Fibronectin binding to thrombin-stimulated platelets was significantly inhibited by P4 but only poorly by P2. These results indicate the presence of specific regions on the glycoprotein IIb-IIIa complex which act as binding sites for fibrinogen or fibronectin. Other authors [Haverstick et al. (1985) Blood 66, 946-952; Ginsberg et al. (1985) J. Biol. Chem. 260, 4133-4138] have shown that a tetrapeptide, Arg-Gly-Asp-Ser, inhibited the binding of fibrinogen, fibronectin, and von Willebrand factor (vWf) to stimulated platelets and that fibrinogen competes with vWf and fibronectin for binding. These findings, together with previous studies, therefore indicate the presence of specific regions as well as a common region in the binding sites for fibrinogen and fibronectin on the IIb-IIIa complex.
D000244:Adenosine Diphosphate; D000911:Antibodies, Monoclonal; D001667:Binding, Competitive; D001792:Blood Platelets / Q000032:analysis*; D005340:Fibrinogen / Q000378:metabolism*; D005353:Fibronectins / Q000097:blood*; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000032:analysis*; D011863:Radioimmunoassay / Q000379:methods; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000032:analysis*; D013917:Thrombin
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D010980:Platelet Membrane Glycoproteins; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D013917:Thrombin