VEGF receptor

{{Main|Vascular endothelial growth factor}}

Vascular endothelial growth factor (VEGF) is an important signaling protein involved in both vasculogenesis (the formation of the circulatory system) and angiogenesis (the growth of blood vessels from pre-existing vasculature). As its name implies, VEGF activity is restricted mainly to cells of the vascular endothelium, although it does have effects on a limited number of other cell types (e.g. stimulation monocyte/macrophage migration). In vitro, VEGF has been shown to stimulate endothelial cell mitogenesis and cell migration. VEGF also enhances microvascular permeability and is sometimes referred to as vascular permeability factor.

Image:VEGF receptors.png

All members of the VEGF family stimulate cellular responses by binding to tyrosine kinase receptors (the VEGFRs) on the cell surface, causing them to dimerize and become activated through transphosphorylation. The VEGF receptors have an extracellular portion consisting of 7 immunoglobulin-like domains, a single transmembrane spanning region and an intracellular portion containing a split tyrosine-kinase domain.

VEGF-A binds to VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1). VEGFR-2 appears to mediate almost all of the known cellular responses to VEGF. The function of VEGFR-1 is less well defined, although it is thought to modulate VEGFR-2 signaling. Another function of VEGFR-1 is to act as a dummy/decoy receptor, sequestering VEGF from VEGFR-2 binding (this appears to be particularly important during vasculogenesis in the embryo). In fact, an alternatively spliced form of VEGFR-1 (sFlt1) is not a membrane bound protein but is secreted and functions primarily as a decoy.{{cite journal | vauthors = Zygmunt T, Gay CM, Blondelle J, Singh MK, Flaherty KM, Means PC, Herwig L, Krudewig A, Belting HG, Affolter M, Epstein JA, Torres-Vázquez J | display-authors = 6 | title = Semaphorin-PlexinD1 signaling limits angiogenic potential via the VEGF decoy receptor sFlt1 | journal = Developmental Cell | volume = 21 | issue = 2 | pages = 301–14 | date = August 2011 | pmid = 21802375 | pmc = 3156278 | doi = 10.1016/j.devcel.2011.06.033 }} A third receptor has been discovered (VEGFR-3), however, VEGF-A is not a ligand for this receptor. VEGFR-3 mediates lymphangiogenesis in response to VEGF-C and VEGF-D.

In addition to binding to VEGFRs, VEGF binds to receptor complexes consisting of both neuropilins and VEGFRs. This receptor complex has increased VEGF signalling activity in endothelial cells (blood vessels).{{cite journal | vauthors = Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M | title = Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor | journal = Cell | volume = 92 | issue = 6 | pages = 735–45 | date = March 1998 | pmid = 9529250 | doi = 10.1016/s0092-8674(00)81402-6 | s2cid = 547080 | doi-access = free }}{{cite journal | vauthors = Herzog B, Pellet-Many C, Britton G, Hartzoulakis B, Zachary IC | title = VEGF binding to NRP1 is essential for VEGF stimulation of endothelial cell migration, complex formation between NRP1 and VEGFR2, and signaling via FAK Tyr407 phosphorylation | journal = Molecular Biology of the Cell | volume = 22 | issue = 15 | pages = 2766–76 | date = August 2011 | pmid = 21653826 | pmc = 3145551 | doi = 10.1091/mbc.E09-12-1061 | url = http://discovery.ucl.ac.uk/1327618/1/Mol._Biol._Cell-2011-Herzog-2766-76.pdf }} Neuropilins (NRP) are pleiotropic receptors and therefore other molecules may interfere with the signalling of the NRP/VEGFR receptor complexes. For example, Class 3 semaphorins compete with VEGF₁₆₅ for NRP binding and could therefore regulate VEGF-mediated angiogenesis.{{cite journal | vauthors = Mecollari V, Nieuwenhuis B, Verhaagen J | title = A perspective on the role of class III semaphorin signaling in central nervous system trauma | journal = Frontiers in Cellular Neuroscience | volume = 8 | pages = 328 | date = 2014 | pmid = 25386118 | pmc = 4209881 | doi = 10.3389/fncel.2014.00328 | doi-access = free }}

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{{reflist}}

• {{MeshName|VEGF+Receptors}}
• {{Proteopedia|Vascular_Endothelial_Growth_Factor_Receptor}} - the Vascular Endothelial Growth Factor Receptor Structure in Interactive 3D

{{Growth factor receptors}}

{{Tyrosine kinases}}

{{Enzymes}}

{{Growth factor receptor modulators}}

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{{DEFAULTSORT:Vegf Receptors}}

Category:Tyrosine kinase receptors

Category:Proteins