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Blood, 15 February 2008, Vol. 111, No. 4, pp. 2036-2045. Prepublished online as a Blood First Edition Paper on December 7, 2007; DOI 10.1182/blood-2007-04-084269. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-04-084269v1 111/4/2036    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sulpice, E. Articles by Merkulova-Rainon, T. Search for Related Content PubMed PubMed Citation Articles by Sulpice, E. Articles by Merkulova-Rainon, T. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Neuropilin-1 and neuropilin-2 act as coreceptors, potentiating proangiogenic activity Eric Sulpice1, Jean Plouët1, Mathieu Bergé1, David Allanic1, Gérard Tobelem1, and Tatyana Merkulova-Rainon1 1 Institut des Vaisseaux et du Sang, Centre de Recherche Cardiovasculaire Lariboisière Inserm U 689; Université Paris VII; AP-HP Lariboisière, Paris, France Neuropilin-1 and -2 (NRP1 and NRP2) are the transmembrane glycoproteins interacting with 2 types of ligands: class III semaphorins and several members of the VEGF family, the main regulators of blood and lymphatic vessel growth. We show here that both NRP1 and NRP2 can also bind hepatocyte growth factor (HGF). HGF is a pleiotropic cytokine and potent proangiogenic molecule that acts on its target cells by binding to the c-met receptor. We found that the N-terminal domain of HGF is involved in the interaction with neuropilins. We demonstrated that invalidation of NRP1 or NRP2 by RNA interference in human umbilical vein endothelial cells (HUVECs) decreased HGF-induced c-met phosphorylation and VEGF-A165– and HGF-mediated intracellular signaling. Accordingly, the disruption of NRP1 or NRP2 binding to VEGF-A165 or HGF with a blocking antibody, decreased the proliferation and migration of endothelial cells. This effect may be further enhanced if VEGF-A165 or HGF binding to both NRP1 and NRP2 was disrupted. Using a mouse Matrigel model, we demonstrated that NRP1 is essential for HGF-mediated angiogenesis in vivo. Our results suggest that, in endothelial cells, both NRP1 and NRP2 function as proangiogenic coreceptors, potentiating the activity of at least 2 major proangiogenic cytokines, VEGF-A165 and HGF. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] B. Larrivee, C. Freitas, S. Suchting, I. Brunet, and A. Eichmann Guidance of Vascular Development: Lessons From the Nervous System Circ. Res., February 27, 2009; 104(4): 428 - 441. [Abstract] [Full Text] [PDF] Y. Glinka and G. J. Prud'homme Neuropilin-1 is a receptor for transforming growth factor {beta}-1, activates its latent form, and promotes regulatory T cell activity J. Leukoc. Biol., July 1, 2008; 84(1): 302 - 310. [Abstract] [Full Text] [PDF]

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