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Blood, 1 November 2008, Vol. 112, No. 9, pp. 3638-3649. Prepublished online as a Blood First Edition Paper on July 29, 2008; DOI 10.1182/blood-2007-12-125856. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-12-125856v1 112/9/3638    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 Kawamura, H. Articles by Claesson-Welsh, L. Search for Related Content PubMed PubMed Citation Articles by Kawamura, H. Articles by Claesson-Welsh, L. 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 in regulation of VEGF-induced activation of p38MAPK and endothelial cell organization Harukiyo Kawamura1,*, Xiujuan Li*, Katsutoshi Goishi2, Laurens A. van Meeteren1, Lars Jakobsson1, Stéphanie Cébe-Suarez3, Akio Shimizu2, Dan Edholm1, Kurt Ballmer-Hofer3, Lena Kjellén4, Michael Klagsbrun2, and Lena Claesson-Welsh1 1 Rudbeck Laboratory, Department of Genetics and Pathology, Uppsala, University, Uppsala, Sweden; 2 Vascular Biology Program/Department of Surgery, Children's Hospital and Harvard Medical School, Boston, MA; 3 Paul Scherrer Institut, Laboratory of Biomolecular Research, Molecular Cell Biology, Villigen-PSI, Switzerland; and 4 Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala, University, Uppsala, Sweden Vascular endothelial growth factor (VEGF)–A regulates vascular development and angiogenesis. VEGF isoforms differ in ability to bind coreceptors heparan sulfate (HS) and neuropilin-1 (NRP1). We used VEGF-A165 (which binds HS and NRP1), VEGF-A121 (binds neither HS nor NRP1), and parapoxvirus VEGF-E-NZ2 (binds NRP1 but not HS) to investigate the role of NRP1 in organization of endothelial cells into vascular structures. All 3 ligands induced similar level of VEGFR-2 tyrosine phosphorylation in the presence of NRP1. In contrast, sprouting angiogenesis in differentiating embryonic stem cells (embryoid bodies), formation of branching pericyte-embedded vessels in subcutaneous matrigel plugs, and sprouting of intersegmental vessels in developing zebrafish were induced by VEGF-A165 and VEGF-E-NZ2 but not by VEGF-A121. Analyses of recombinant factors with NRP1-binding gain- and loss-of-function properties supported the conclusion that NRP1 is critical for VEGF-induced sprouting and branching of endothelial cells. Signal transduction antibody arrays implicated NRP1 in VEGF-induced activation of p38MAPK. Inclusion of the p38MAPK inhibitor SB203580 in VEGF-A165–containing matrigel plugs led to attenuated angiogenesis and poor association with pericytes. Our data strongly indicate that the ability of VEGF ligands to bind NRP1 influences p38MAPK activation, and formation of functional, pericyte-associated vessels. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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]

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