Neuropilin-1-mediated vascular permeability factor/vascular endothelial growth factor-dependent endothelial cell migration.

Ling Wang, Huiyan Zeng, Ping Wang, Shay Soker, Debabrata Mukhopadhyay

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

Neuropilin-1 (NRP-1) has been found to be expressed by endothelial cells and tumor cells as an isoform-specific receptor for vascular permeability factor/vascular endothelial growth factor (VEGF). Previous studies were mainly focused on the extracellular domain of NRP-1 that can bind to VEGF165 and, thus, enables NRP-1 to act as a co-receptor for VEGF165, which enhances its binding to VEGFR-2 and its bioactivity. However, the exact functional roles and related signaling mechanisms of NRP-1 in angiogenesis are not well understood. In this study we constructed a chimeric receptor, EGNP-1, by fusing the extracellular domain of epidermal growth factor receptor to the transmembrane and intracellular domains of NRP-1 and transduced it into HUVECs with a retroviral expression vector. We observed that NRP-1/EGNP-1 mediates ligand-stimulated migration of human umbilical vein endothelial cells (HUVECs) but not proliferation. Our results show that NRP-1 alone can mediate HUVEC migration through its intracellular domain, and its C-terminal three amino acids (SEA-COOH) are essential for the process. We demonstrate that phosphatidylinositol 3-kinase inhibitor Ly294002 and the p85 dominant negative mutant can block NRP-1-mediated HUVEC migration. NRP-1-mediated migration can be significantly reduced by overexpression of the dominant negative mutant of RhoA (RhoA-19N). In addition, Gq family proteins and Gbetagamma subunits are also required for NRP-1-mediated HUVEC migration. These results show for the first time that NRP-1 can independently promote cell signaling in endothelial cells and also demonstrate the importance of last three amino acids of NRP-1 for its function.

Original languageEnglish (US)
Pages (from-to)48848-48860
Number of pages13
JournalThe Journal of biological chemistry
Volume278
Issue number49
StatePublished - Dec 5 2003
Externally publishedYes

Fingerprint

Neuropilin-1
Endothelial cells
Vascular Endothelial Growth Factor A
Cell Movement
Endothelial Cells
Human Umbilical Vein Endothelial Cells
Gq-G11 GTP-Binding Protein alpha Subunits
Phosphatidylinositol 3-Kinase
Cell signaling
Amino Acids
Vascular Endothelial Growth Factor Receptor-2
Vascular Endothelial Growth Factor Receptor
Protein Subunits
Bioactivity
Epidermal Growth Factor Receptor

ASJC Scopus subject areas

  • Biochemistry

Cite this

Neuropilin-1-mediated vascular permeability factor/vascular endothelial growth factor-dependent endothelial cell migration. / Wang, Ling; Zeng, Huiyan; Wang, Ping; Soker, Shay; Mukhopadhyay, Debabrata.

In: The Journal of biological chemistry, Vol. 278, No. 49, 05.12.2003, p. 48848-48860.

Research output: Contribution to journalArticle

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