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A tripeptide mimetic of von Willebrand factor residues 981–983 enhances platelet adhesion to fibrinogen by signaling through integrin β IIb β 3
Author(s) -
LITJENS P. E. M. H.,
WILLIGEN G.,
WEETERINGS C.,
IJSSELDIJK M. J. W.,
LIER M.,
KOIVUNEN E.,
GAHMBERG C. G.,
AKKERMAN J. W. N.
Publication year - 2005
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2005.01408.x
Subject(s) - tripeptide , platelet , chemistry , integrin , von willebrand factor , platelet activation , biochemistry , syk , platelet adhesiveness , tyrosine , microbiology and biotechnology , peptide , biology , tyrosine kinase , immunology , signal transduction , receptor , platelet aggregation
Summary. Background: RGD is a major recognition sequence for ligands of platelet α IIb β 3 . Objective and methods: To identify potential binding sites for α IIb β 3 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 α IIb β 3 ‐dependent manner; platelets and α IIb β 3 ‐expressing CHO cells adhered faster to immobilized α IIb β 3 ‐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 α IIb β 3 ‐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. Conclusion: These data reveal a VPW sequence that contributes to α IIb β 3 activation in in vitro experiments. Whether the V980–P981‐W982 sequence in vWf shows similar properties under in vivo conditions remains to be established.