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

  title={A VEGF-A splice variant defective for heparan sulfate and neuropilin-1 binding shows attenuated signaling through VEGFR-2},
  author={S. C{\'e}be Suarez and Michel Pieren and Luca Cariolato and S. Arn and Udo Hoffmann and Augustyn Bogucki and Corinne Manlius and Jeanette Marjorie Wood and Kurt Ballmer-Hofer},
  journal={Cellular and Molecular Life Sciences CMLS},
Abstract.The development of functional blood and lymphatic vessels requires spatio-temporal coordination of the production and release of growth factors such as vascular endothelial growth factors (VEGFs). VEGF family proteins are produced in multiple isoforms with distinct biological properties and bind to three types of VEGF receptors. A VEGF-A splice variant, VEGF-A165b, has recently been isolated from kidney epithelial cells. This variant is identical to VEGF-A165 except for the last six… 

VEGF-A121a binding to Neuropilins – A concept revisited

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VEGF-A splice variants bind VEGFRs with differential affinities

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It is shown that loss of V EGFR-2/NRP1 complex formation and Y1052 phosphorylation contribute to the lack of angiogenic properties of VEGF-A165b.

Molecular Pharmacology of VEGF-A Isoforms: Binding and Signalling at VEGFR2

To understand how VEGF-A isoforms have distinct signalling despite similar affinities for VEGFR2, this review re-evaluates the typical classification of these isoforms relative to the prototypical, “pro-angiogenic” V EGF165a.

Neuropilin-1 in regulation of VEGF-induced activation of p38MAPK and endothelial cell organization.

The data strongly indicate that the ability of VEGF ligands to bind NRP1 influences p38MAPK activation, and formation of functional, pericyte-associated vessels.

VEGF165b, a splice variant of VEGF-A, promotes lung tumor progression and escape from anti-angiogenic therapies through a β1 integrin/VEGFR autocrine loop

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VEGF111b, a new member of VEGFxxxb isoforms and induced by mitomycin C, inhibits angiogenesis.

Molecular Diversity of VEGF‐A as a Regulator of Its Biological Activity

The molecular diversity of VEGF‐A is examined as a regulator of its biological activity and the role of the pro‐ and antiangiogenic VEGf‐A splice isoforms in both normal and pathophysiological processes are compared.



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.

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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.

VEGF165b, an Inhibitory Vascular Endothelial Growth Factor Splice Variant

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Glypican-1 Is a VEGF165 Binding Proteoglycan That Acts as an Extracellular Chaperone for VEGF165 *

It is suggested that glypican-1 may play an important role in the control of angiogenesis by regulating the activity of VEGF165, a regulation that may be critical under conditions such as wound repair, in which oxidizing agents that can impair theActivity of V EGF are produced, and in situations were the concentrations of active VEGf are limiting.

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.

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VEGF121, a vascular endothelial growth factor (VEGF) isoform lacking heparin binding ability, requires cell-surface heparan sulfates for efficient binding to the VEGF receptors of human melanoma cells

Results suggest that cell-surface heparan sulfates may regulate the binding ability of the VEGF receptors of the melanoma cells and indicate that heparin is not able to fully substitute for cell surface-associated heparAn sulfates.

Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells.

The binding of VEGF-B to its receptor on endothelial cells leads to increased expression and activity of urokinase type plasminogen activator and plasmineg activator inhibitor 1, suggesting a role for VEGf-B in the regulation of extracellular matrix degradation, cell adhesion, and migration.