title: A tripeptide mimetic of von Willebrand factor residues 981-983 enhances platelet adhesion to fibrinogen by signaling through integrin alpha(IIb)beta3.
abstract: BACKGROUND
  RGD is a major recognition sequence for ligands of platelet alpha(IIb)beta3.
  
  
  OBJECTIVE
  To identify potential binding sites for alpha(IIb)beta3 apart from RGD, we screened phage display libraries by blocking the enrichment of RGD-containing phages with a GRGDS peptide and identified a novel integrin recognition tripeptide sequence, VPW.
  
  
  RESULTS
  Platelets adhered to an immobilized cyclic VPW containing peptide in a alpha(IIb)beta3-dependent manner; platelets and alpha(IIb)beta3-expressing CHO cells adhered faster to immobilized alpha(IIb)beta3-ligands in the presence of soluble VPW. In platelets adhering to fibrinogen, VPW accelerated the activation of the tyrosine kinase Syk which controls cytoskeletal rearrangements. In alpha(IIb)beta3-expressing CHO cells, VPW induced a faster formation of stress fibers. Sequence alignment positioned VPW to V980-P981-W982 in the von Willebrand factor (vWf) A-3 domain. In blood from a vWf-deficient individual, VPW increased platelet adhesion to fibrinogen but not to collagen under flow and rescued the impaired adhesion to vWf deficient in A-3.
  
  
  CONCLUSIONS
  These data reveal a VPW sequence that contributes to alpha(IIb)beta3 activation in in vitro experiments. Whether the V980-P981-W982 sequence in vWf shows similar properties under in vivo conditions remains to be established.
authors.affiliation: Laboratory for Thrombosis and Haemostasis, Department of Haematology, UMCU, and Institute for Biomembranes, Utrecht University, Utrecht, The Netherlands.
authors.forename: P E M H
authors.initials: PE
authors.lastname: Litjens
authors.forename: G
authors.initials: G
authors.lastname: Van Willigen
authors.forename: C
authors.initials: C
authors.lastname: Weeterings
authors.forename: M J W
authors.initials: MJ
authors.lastname: Ijsseldijk
authors.forename: M
authors.initials: M
authors.lastname: Van Lier
authors.forename: E
authors.initials: E
authors.lastname: Koivunen
authors.forename: C G
authors.initials: CG
authors.lastname: Gahmberg
authors.forename: J W N
authors.initials: JW
authors.lastname: Akkerman
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D001792:Blood Platelets; D004792:Enzyme Precursors / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase; D014842:von Willebrand Diseases / Q000097:blood; D014841:von Willebrand Factor / Q000031:analogs & derivatives* / Q000737:chemistry / Q000502:physiology
chemical_list: D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014841:von Willebrand Factor; D005340:Fibrinogen; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase