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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3479-3488. Prepublished online as a Blood First Edition Paper on January 9, 2008; DOI 10.1182/blood-2007-03-077537. This Article Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2007-03-077537v1 111/7/3479    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Soro, S. Articles by Failla, C. M. Search for Related Content PubMed PubMed Citation Articles by Soro, S. Articles by Failla, C. M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 2, 2007 Accepted December 18, 2007 A proangiogenic peptide derived from vascular endothelial growth factor receptor-1 acts through 51 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 Tramontano, and Cristina Maria Failla* Dept of Biochemical Sciences "A. Rossi Fanelli", University "La Sapienza", Rome, Italy Molecular and Cell Biology Laboratory, IDI-IRCCS, Rome, Italy Deptartment of Molecular Biology, University of Siena, Siena, Italy Molecular Oncology Laboratory, IDI-IRCCS, Rome, Italy CNR Institute of Molecular Biology and Pathology, University "La Sapienza", Rome, Italy Biomolecular Research, Molecular Cell Biology, Paul Scherrer Institut, Villigen, Switzerland Istituto Pasteur-Fondazione Cenci Bolognetti, University "La Sapienza", Rome, Italy * Corresponding author; email: c.failla{at}idi.it. 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 extracellular matrix produced by endothelial cells in culture and is able to promote cell adhesion and migration through binding to 51 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 51 integrin. To identify domain regions involved in integrin binding, we designed twelve peptides putatively mimicking the domain II surface and tested their ability to inhibit 51-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 towards soluble VEGFR-1 as well. This peptide directly binds 51 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 biological activity and integrin binding. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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