title: A novel role for the fibrinogen Asn-Gly-Arg (NGR) motif in platelet function.
abstract: The integrin αIIbβ3 on resting platelets can bind to immobilised fibrinogen resulting in platelet spreading and activation but requires activation to bind to soluble fibrinogen. αIIbβ3 is known to interact with the general integrin-recognition motif RGD (arginine-glycine-aspartate) as well as the fibrinogen-specific γ-chain dodecapeptide; however, it is not known how fibrinogen binding triggers platelet activation. NGR (asparagine-glycine-arginine) is another integrin-recognition sequence present in fibrinogen and this study aims to determine if it plays a role in the interaction between fibrinogen and αIIbβ3. NGR-containing peptides inhibited resting platelet adhesion to fibrinogen with an IC50 of 175 µM but failed to inhibit the adhesion of activated platelets to fibrinogen (IC50> 500 µM). Resting platelet adhesion to mutant fibrinogens lacking the NGR sequences was reduced compared to normal fibrinogen under both static and shear conditions (200 s⁻¹). However, pre-activated platelets were able to fully spread on all types of fibrinogen. Thus, the NGR motif in fibrinogen is the site that is primarily responsible for the interaction with resting αIIbβ3 and is responsible for triggering platelet activation.
authors.forename: Róisín
authors.initials: R
authors.lastname: Moriarty
authors.forename: Ciara A
authors.initials: CA
authors.lastname: McManus
authors.forename: Matthew
authors.initials: M
authors.lastname: Lambert
authors.forename: Thea
authors.initials: T
authors.lastname: Tilley
authors.forename: Marc
authors.initials: M
authors.lastname: Devocelle
authors.forename: Marian
authors.initials: M
authors.lastname: Brennan
authors.forename: Steven W
authors.initials: SW
authors.lastname: Kerrigan
authors.affiliation: Dermot Cox, BSc, PhD, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2, Ireland, Tel.: +35 3 1 402 2152, Fax: +35 3 1 402 2453, E-mail: dcox@rcsi.ie.
authors.forename: Dermot
authors.initials: D
authors.lastname: Cox
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001777:Blood Coagulation; D001792:Blood Platelets / Q000502:physiology*; D018826:CD13 Antigens / Q000737:chemistry; D016466:CHO Cells; D019556:COS Cells; D002448:Cell Adhesion; D002522:Chlorocebus aethiops; D003412:Cricetulus; D004797:Enzyme-Linked Immunosorbent Assay; D005340:Fibrinogen / Q000737:chemistry*; D064368:Healthy Volunteers; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009842:Oligopeptides / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation / Q000502:physiology; D010979:Platelet Function Tests; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry*; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D008024:Ligands; C526428:NGR peptide; D009842:Oligopeptides; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins; D011994:Recombinant Proteins; D005340:Fibrinogen; D018826:CD13 Antigens
keywords: GPIIb-IIIa; Platelets; fibrinogen; platelet activation