SEARCH:   Advanced

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 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 Citation Map 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. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY A proangiogenic peptide derived from vascular endothelial growth factor receptor-1 acts through 5β1 integrin Simonetta Soro1, Angela Orecchia2, Lucia Morbidelli3, Pedro Miguel Lacal4, Veronica Morea5, Kurt Ballmer-Hofer6, Federica Ruffini4, Marina Ziche3, Stefania D'Atri4, Giovanna Zambruno2, Anna Tramontano1,7, and Cristina Maria Failla2 1 Department of Biochemical Sciences A. Rossi Fanelli, University La Sapienza, Rome, Italy; 2 Molecular and Cell Biology Laboratory, Istituto Dermopatico dell'Immacolata-Istituto di Ricovero e Cura a Carattere Scientifico (IDI-IRCCS), Rome, Italy; 3 Department of Molecular Biology, University of Siena, Siena, Italy; 4 Molecular Oncology Laboratory, IDI-IRCCS, Rome, Italy; 5 National Reseach Council (CNR) Institute of Molecular Biology and Pathology, University La Sapienza, Rome, Italy; 6 Paul Scherrer Institut (PSI), Biomolecular Research, Molecular Cell Biology, Villigen-PSI, Switzerland; and 7 Istituto Pasteur-Fondazione Cenci Bolognetti, University La Sapienza, Rome, Italy 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 5β1 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 5β1 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 5β1-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 5β1 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020