In contrast to fibrinogen or fibrin, peptide and peptide mimetic binding to alpha does not cause outside-in signalling as judged by measurements of phosphatidylinositol 4,5-bisphosphate beta (GPIIb-IIIa) IIb 3
Journal Articles
Overview
Research
Identity
Additional Document Info
View All
Overview
abstract
Binding of ligands, including RGD-containing peptides, to the platelet fibrinogen receptor, integrin alphaIIb beta3 has been reported to cause outside-in signals, which result in clustering of occupied receptors and changes in conformation of the receptor and its cytoplasmic tails. Thus, the peptides that are usually used as inhibitors may function as partial agonists. Binding of ligand, fibrinogen or polymerizing fibrin, to platelets with activated alphaIIbbeta3 causes decreases in phosphatidylinositol 4,5-bisphosphate (PIP ), which may affect actin organization. Whether or not binding to unactivated platelets of the peptide RGDS, the fibrinogen gamma -chain C-terminal dodecapeptide (H12), or a high affinity RGD mimetic SC-54701B affects phosphoinositide metabolism was tested. Although incubation of RGDS (230 microM), dodecapeptide (400 microM) or SC-54701B (10 microM) with platelets for 2 min caused trends towards decreases in PIP , no significant decreases were found. As a positive control, 2 SC-54701B was shown to inhibit the decrease in PIP in ADP-stimulated platelets at concentrations consistent 2 with the reported IC50 of 0.12 microM. Thus, binding of peptides or the high affinity RGD mimetic does not 50 generate a sufficient signal to affect the signalling pathway that is involved phosphoinositide metabolism.
