Effect of cyclic Arg-Gly-Asp-containing peptide on fibronectin binding to activated platelets; role of fibronectin on platelet aggregation.
The interaction of fibronectin with glycoprotein IIb/IIIa (GPIIb/IIIa) was studied. Fibronectin bound to thrombin-stimulated platelets in a calcium-dependent, specific, and saturable manner with 98,000 molecules/platelet (Kd = 2.76 x 10(-7) M). The binding was inhibited by other adhesive proteins with IC50S of 0.076-0.105 microM and the anti-GPIIb/IIIa monoclonal antibody (LJ-CP8). The binding was also inhibited by the cyclic GRGDSPA peptide and the linear GRGDSPA peptide with IC50S of 0.223 microM and 3.75 microM, respectively. Native fibronectin, the cyclic peptide, and the linear peptide blocked thrombin-induced aggregation with IC50 of 0.95 microM, 32 microM, and 190 microM, respectively. These observations imply that the conformation of RGD-containing sequence may play an important role for an increasing affinity of the binding, and fibronectin may prevent thrombus formation by interfering with the interaction between fibrinogen and activated GPIIb/IIIa.
Mohri
H
H
First Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Ohkubo
T
T
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D005353:Fibronectins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D015539:Platelet Activation / Q000502:physiology; D010973:Platelet Adhesiveness / Q000502:physiology; D010974:Platelet Aggregation / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011485:Protein Binding; D013917:Thrombin
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D010980:Platelet Membrane Glycoproteins; D013917:Thrombin