Neuropilin-1 Is Expressed by Endothelial and Tumor Cells as an Isoform-Specific Receptor for Vascular Endothelial Growth Factor

  title={Neuropilin-1 Is Expressed by Endothelial and Tumor Cells as an Isoform-Specific Receptor for Vascular Endothelial Growth Factor},
  author={Shay Soker and Seiji Takashima and Hua Miao and Gera Neufeld and Michael Klagsbrun},

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Neuropilin-1-mediated Vascular Permeability Factor/Vascular Endothelial Growth Factor-dependent Endothelial Cell Migration*

This study 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 and showed for the first time that N RP-1 can independently promote cell signaling in endothelial cells.

Selective induction of neuropilin-1 by vascular endothelial growth factor (VEGF): A mechanism contributing to VEGF-induced angiogenesis

  • H. OhH. Takagi Y. Honda
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2001
The results suggest that VEGF cannot only activate endothelial cells directly but also can contribute to robust angiogenesis in vivo by a mechanism that involves up-regulation of its cognate receptor expression.

Vascular Endothelial Growth Factor Receptor-2 and Neuropilin-1 Form a Receptor Complex That Is Responsible for the Differential Signaling Potency of VEGF165 and VEGF121 *

It is demonstrated that although VEGFR-2 and Npn-1 form a complex, this complex does not result in an increase in VEGF165 binding affinity, and data suggest a receptor-clustering role for NPN-1, as opposed to Npn -1 behaving as an affinity-converting subunit.

Neuropilin-2 interacts with VEGFR-2 and VEGFR-3 and promotes human endothelial cell survival and migration.

The data indicate that NRP2 acts as a coreceptor that enhances human endothelial cell biological responses induced by VEGF-A and VEGf-C, and is correlated with an enhancement of the VEGFR-2 phosphorylation threshold.

Neuropilin-1 regulates attachment in human endothelial cells independently of vascular endothelial growth factor receptor-2.

Based on its dual role as an enhancer of VEGF activity and a mediator of endothelial cell adhesiveness described here, NRP-1 emerges as a promising molecular target for the development of antiangiogenic drugs.

Neuropilin-1 Binds to VEGF121 and Regulates Endothelial Cell Migration and Sprouting*

It is reported that blocking NRP1 function, using a recently described antibody that inhibits VEGF165 binding to N RP1, surprisingly reduces V EGF121-induced migration and sprout formation of endothelial cells.

Structural Basis for Selective Vascular Endothelial Growth Factor-A (VEGF-A) Binding to Neuropilin-1*

The structural basis for selective VEGF-A splice form binding to neuropilin is established and it is demonstrated that the exon 8-encoded C-terminal arginine is essential for the interaction of VEGf-A with Nrp1 and mediates high affinity NrP binding.

A VEGF-A splice variant defective for heparan sulfate and neuropilin-1 binding shows attenuated signaling through VEGFR-2

VEGF-A165b has attenuated signaling potential through VEGF receptor 2 defining this new member of the V EGF family as a partial receptor agonist.

The splice variants of vascular endothelial growth factor (VEGF) and their receptors.

Vascular endothelial growth factor (VEGF) is a secreted mitogen highly specific for cultured endothelial cells and plays a central role in both angiogenesis and vasculogenesis, most notably the neovascularisation of growing tumours.

Neuropilin-1 Regulates Vascular Endothelial Growth Factor–Mediated Endothelial Permeability

A critical role for Npn-1 is supported in regulating endothelial barrier dysfunction in response to VEGF and activation of distinct receptor complexes may determine specificity of cellular response toVEGF is suggested.



VEGF145, a Secreted Vascular Endothelial Growth Factor Isoform That Binds to Extracellular Matrix*

Recombinant VEGF145 induced the proliferation of vascular endothelial cells and promoted angiogenesis in vivo and seems to possess a unique combination of biological properties distinct from those of previously characterized V EGF species.

Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor.

Identification of Vascular Endothelial Growth Factor Determinants for Binding KDR and FLT-1 Receptors

Results suggest dual sets of determinants in the VEGF dimer that cross-link cell surface receptors, triggering endothelial cell growth and angiogenesis and implicates KDR, but not FLT-1, in V EGF induction of endothelialcell proliferation.

High levels of biologically active vascular endothelial growth factor (VEGF) are produced by the baculovirus expression system.

InVEGF is biologically active and induces the proliferation of human umbilical vein derived endothelial cells and competes with pure mammalian cells derived [125I]-VEGF for binding to the VEGF receptors that are present on the cell surface of endothelial Cells.

Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1.

The results presented here suggest that monocyte chemotaxis in response to VEGF and most likely to Placenta growth factor is mediated by flt-1 and thus show a possible function for the V EGF-receptor flT-1.

Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms.

Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor.

  • R. KendallK. Thomas
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1993
The recombinant soluble human receptor binds vascular endothelial cell growth factor with high affinity and inhibits its mitogenic activity forascular endothelial cells; thus this soluble receptor could act as an efficient specific antagonist of vascular endothelium cell growthFactor in vivo.

The Carboxyl-terminal Domain(111165) of Vascular Endothelial Growth Factor Is Critical for Its Mitogenic Potency (*)

The present findings indicate that removal of the carboxyl-terminal domain, whether it is due to alternative splicing of mRNA or to proteolysis, is associated with a significant loss in bioactivity.

The binding of vascular endothelial growth factor to its receptors is dependent on cell surface-associated heparin-like molecules.