A proangiogenic peptide derived from vascular endothelial growth factor receptor-1 acts through {alpha}5{beta}1 integrin

Simonetta Soro, Angela Orecchia, Lucia Morbidelli, Pedro Miguel Lacal, Veronica Morea, Kurt Ballmer-Hofer, Federica Ruffini, Marina Ziche, Stefania D'Atri, Giovanna Zambruno, Anna Tramontane, Cristina Maria Failla

Research output: Contribution to journalArticlepeer-review


Vascular endothelial growth factor receptor-1 (VEGFR-1) is a tyrosine kinase receptor for growth factors of the VEGF family. Endothelial cells express a membrane-bound and a soluble variant of this protein, the latter being mainly considered as a negative regulator of VEGF-A signaling. We previously reported that the soluble form is deposited in the extra-cellular matrix produced by endothelial cells in culture and is able to promote cell adhesion and migration through binding to α5β1 integrin. In this study, we demonstrate that the Ig-like domain II of VEGFR-1, which contains the binding determinants for the growth factors, is involved in the interaction with α5β1 integrin. To identify domain regions involved in integrin binding, we designed 12 peptides putatively mimicking the domain II surface and tested their ability to inhibit α5β1-mediated endothelial cell adhesion to soluble VEGFR-1 and directly support cell adhesion. One peptide endowed with both these properties was identified and shown to inhibit endothelial cell migration toward soluble VEGFR-1 as well. This peptide directly binds α5β1 integrin, but not VEGF-A, inducing endothelial cell tubule formation in vitro and neoangiogenesis in vivo. Alanine scanning mutagenesis of the peptide defined which residues were responsible for its biologic activity and integrin binding.

Original languageEnglish
Pages (from-to)3479-3488
Number of pages10
Issue number7
Publication statusPublished - Apr 1 2008

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology


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