SEARCH:   Advanced

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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 6, 2007 Accepted December 3, 2007 Neuropilin-1 and neuropilin-2 act as coreceptors, potentiating proangiogenic activity Eric Sulpice, Jean Plouet, Mathieu Berge, David Allanic, Gerard Tobelem, and Tatyana Merkulova-Rainon* Institute des Vaisseaux et du Sang, Centre de Recherche Cardiovasculaire Lariboisere INSERM U 689, Universite Paris VII, AP-HP Lariboisere, Paris, France * Corresponding author; email: merkoulova{at}larib.inserm.fr. Neuropilins (NRP1 and NRP2) are the transmembrane glycoproteins interacting with two 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 HUVEC 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 two 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: S. D. Robinson, L. E. Reynolds, V. Kostourou, A. R. Reynolds, R. G. da Silva, B. Tavora, M. Baker, J. F. Marshall, and K. M. Hodivala-Dilke {alpha}v{beta}3 Integrin Limits the Contribution of Neuropilin-1 to Vascular Endothelial Growth Factor-induced Angiogenesis J. Biol. Chem., December 4, 2009; 284(49): 33966 - 33981. [Abstract] [Full Text] [PDF] A. Le, R. Zielinski, C. He, M. T. Crow, S. Biswal, R. M. Tuder, and P. M. Becker Pulmonary Epithelial Neuropilin-1 Deletion Enhances Development of Cigarette Smoke-induced Emphysema Am. J. Respir. Crit. Care Med., September 1, 2009; 180(5): 396 - 406. [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] 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] D. Bae, S. Lu, C. A. Taglienti, and A. M. Mercurio Metabolic Stress Induces the Lysosomal Degradation of Neuropilin-1 but Not Neuropilin-2 J. Biol. Chem., October 17, 2008; 283(42): 28074 - 28080. [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]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020