Fibrinogen binds to integrin α5β1 via the Carboxyl-terminal RGD site of the Aα-chain

Kazuhisa Suehiro, Jun Mizuguchi, Kiyoto Nishiyama, Sadaaki Iwanaga, David H. Farrell, Sachiya Ohtaki

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Fibrinogen interactions with vascular endothelial cells are implicated in various physiological and pathophysiological events, including angiogenesis and wound healing. We have shown previously that integrin α5β1 is a fibrinogen receptor on endothelial cells [Suehiro, K., Gailit, J., and Plow, E.F. (1997) J. Biol. Chem. 272, 5360-5366]. In the present study, we have characterized fibrinogen interactions with purified α5β1 and have identifled the recognition sequence in fibrinogen for α5β1. The binding of fibrinogen to immobilized α5β1 was selectively supported by Mn2+. Fibrinogen bound to purified α5β1 in a time-dependent, specific, and saturable manner in the presence of Mn2+, and the binding was blocked completely by Arg-Gly-Asp (RGD)-containing peptides and by anti-α5 and anti-α5β1 monoclonal antibodies. A monoclonal antibody directed to the C-termlnal RGD sequence at Aα572-574 significantly inhibited the binding of fibrinogen to α5β1, whereas monoclonal antibodies directed to either the N-terminal RGD sequence at Aα95-97 or the C-terminus of the γ-chain did not. Furthermore, substituting RGE for RGD at position Aα95-97 in recombinant fibrinogen had a minimal effect on binding, whereas substituting RGE for RGD at position Aα572-574 decreased binding by 90%. These results demonstrate that the C-terminal RGD sequence at Aα572-574 is required for the interaction of fibrinogen with α5β1.

Original languageEnglish (US)
Pages (from-to)705-710
Number of pages6
JournalJournal of Biochemistry
Volume128
Issue number4
DOIs
StatePublished - Jan 1 2000

Keywords

  • Divalent cations
  • Fibrinogen
  • Fibronectin receptor
  • Integrin
  • RGD

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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