Developmental Signals - Vascular Endothelial Growth Factor

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Introduction

Vascular endothelial growth factor (VEGF) secreted protein growth factor family which stimulates the proliferation of vasular endotheial cells and therefore blood vessel growth.

VEGF is secreted but remains associated with cells or extracellular matrix. It is released by heparin. VEGF belongs to the platelet derive growth factor (PDGF) family, has four isoforms are formed by alternative splicing of the same gene.


Factor Links: AMH | hCG | BMP | sonic hedgehog | bHLH | HOX | FGF | FOX | Hippo | LIM | Nanog | NGF | Nodal | Notch | PAX | retinoic acid | SIX | Slit2/Robo1 | SOX | TBX | TGF-beta | VEGF | WNT | Category:Molecular

| Category:VEGF | Blood Vessel Development

Some Recent Findings

  • Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting[1]

Structure

Gene

Protein

Vascular endothelial growth factor A

  • Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth.
  • Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels.
  • Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin.

Vascular endothelial growth factor receptor 2

  • Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD.
  • Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis.

Function

Signaling Pathway

Arterial Differentiation "Two 2002 papers in Cell and Developmental Cell provide evidence that VEGF directs arterial differentiation. Evidence that sensory nerves direct arteriogenesis (Mukouyama et al., 2002) and that the membrane spanning Notch signaling system is downstream of VEGF (Lawson et al., 2002) emphasize the paracrine regulation of vessel formation."

Model shown in Figure 1. Shh/VEGF/Notch in the Arterial Vasculature Sonic hedgehog (Shh) binding to the receptor complex formed by Patched (Ptc) and Smoothened (Smo) can release the inhibition of Smo by Ptc. The derepressed Smo in turn activates the Gli family of transcription factors. Shh can upregulate the expression of VEGF by mesenchymal cells, but whether the Ptc/Smo/Gli pathway is involved in this Shh-mediated VEGF production is still unclear. VEGF acts on its specific receptors, including Flk-1 and neuropilin-1 (NP-1) and induces arterial-specific EphrinB2 expression on endothelial cells (EC). However, VEGF-induced EphrinB2 expression is dependent on the Notch signaling pathway, and it is unclear (?) if VEGF can activate the Notch pathway in arterial ECs directly. Both the Notch receptor family and their ligand (Delta and Jagged) families are expressed by the EC and smooth muscle cell (SMC)/pericyte in vivo.

(from: Won't You Be My Neighbor? Local Induction of Arteriogenesis Cell, Vol. 110, 289-292, August 9, 2002)

Receptor

Intracellular Signaling

Vascular Endothelial Protein Tyrosine Phosphatase

This phosphatase is involved in vascular development through modulation of a receptor tyrosine kinase (Tie2) activity, the receptor of angiopoietin. Phosphatases remove and kinases add a phosphate group to proteins, phosphorylation is a common intracellular signaling pathway.


OMIM

About OMIM "Online Mendelian Inheritance in Man OMIM is a comprehensive, authoritative, and timely compendium of human genes and genetic phenotypes. The full-text, referenced overviews in OMIM contain information on all known mendelian disorders and over 12,000 genes. OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries contain copious links to other genetics resources." OMIM


References

  1. <pubmed>17296940</pubmed>

Reviews

Articles

<pubmed>22693607</pubmed>

Online Textbooks

  • Molecular Biology of the Cell. 4th edition. Alberts B, Johnson A, Lewis J, et al.New York: Garland Science; 2002.
  • Molecular Cell Biology. 4th edition. Lodish H, Berk A, Zipursky SL, et al.New York: W. H. Freeman; 2000.
  • Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000.

Search PubMed

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Cite this page: Hill, M.A. (2021, June 24) Embryology Developmental Signals - Vascular Endothelial Growth Factor. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Developmental_Signals_-_Vascular_Endothelial_Growth_Factor

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