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Blood, 15 May 2006, Vol. 107, No. 10, pp. 3892-3901. Prepublished online as a Blood First Edition Paper on January 19, 2006; DOI 10.1182/blood-2005-10-4113. This Article Full Text (PDF) All Versions of this Article: 2005-10-4113v1 107/10/3892    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Narazaki, M. Articles by Tosato, G. Search for Related Content PubMed PubMed Citation Articles by Narazaki, M. Articles by Tosato, G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 14, 2005 Accepted January 8, 2006 Ligand-induced internalization selects usage of common receptor Neuropilin-1 by VEGF165 and Semaphorin3A Masashi Narazaki* and Giovanna Tosato Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA * Corresponding author; email: narazakm{at}mail.nih.gov. Neuropilin-1 (Npn-1) is a receptor shared by class 3 semaphorins and heparin- binding forms of vascular endothelial growth factor (VEGF), protein families that regulate endothelial and neuronal cell function. Ligand interaction with Npn-1 dictates the choice of signal transducer: plexins transduce semaphorin signals and VEGF receptors transduce VEGF signals. It is not clear how class 3 semaphorins affect endothelial cell function and how the shared receptor Npn-1 selects its ligand. We report that Semaphorin3A (Sema3A) inhibits endothelial cell lamellipodia formation, adhesion, survival, proliferation, and cord formation. VEGF165, but not VEGF121, could block all these effects of Sema3A. VEGF165 competed with Sema3A for binding to endothelial cells, effectively reduced cell surface Npn-1, and promoted its internalization. Use of soluble forms of Npn-1 or VEGF receptor-1 to block VEGF165 binding to Npn-1 or to VEGF receptors provided evidence that surface Npn-1 and VEGF receptors are required for VEGF165-induced Npn-1 internalization. Sema3A also reduced cell surface Npn-1 in endothelial cells and promoted its internalization, but required a higher concentration than VEGF165. These results demonstrate that preferential receptor binding and internalization by a ligand are mechanisms by which the common receptor Npn-1 can play an essential role in prioritizing conflicting signals. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Gaur, D. R. Bielenberg, S. Samuel, D. Bose, Y. Zhou, M. J. Gray, N. A. Dallas, F. Fan, L. Xia, J. Lu, et al. Role of Class 3 Semaphorins and Their Receptors in Tumor Growth and Angiogenesis Clin. Cancer Res., November 15, 2009; 15(22): 6763 - 6770. [Abstract] [Full Text] [PDF] L. Capparuccia and L. Tamagnone Semaphorin signaling in cancer cells and in cells of the tumor microenvironment - two sides of a coin J. Cell Sci., June 1, 2009; 122(11): 1723 - 1736. [Abstract] [Full Text] [PDF] C. Ruiz de Almodovar, D. Lambrechts, M. Mazzone, and P. Carmeliet Role and Therapeutic Potential of VEGF in the Nervous System Physiol Rev, April 1, 2009; 89(2): 607 - 648. [Abstract] [Full Text] [PDF] S. Sakakibara, C. A. Pise-Masison, J. N. Brady, and G. Tosato Gene Regulation and Functional Alterations Induced by Kaposi's Sarcoma-Associated Herpesvirus-Encoded ORFK13/vFLIP in Endothelial Cells J. Virol., March 1, 2009; 83(5): 2140 - 2153. 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