Vascular endothelial growth factor (VEGF) is an important signalingprotein involved in bothvasculogenesis (the formation of thecirculatory system) andangiogenesis (the growth of blood vessels from pre-existing vasculature). As its name implies, VEGF activity is restricted mainly to cells of the vascularendothelium, although it does have effects on a limited number of other cell types (e.g. stimulationmonocyte/macrophage migration).In vitro, VEGF has been shown to stimulate endothelial cellmitogenesis andcell migration. VEGF also enhances microvascular permeability and is sometimes referred to as vascular permeability factor.
All members of the VEGF family stimulate cellular responses by binding totyrosine kinase receptors (the VEGFRs) on the cell surface, causing them to dimerize and become activated throughtransphosphorylation. The VEGF receptors have an extracellular portion consisting of 7immunoglobulin-like domains, a single transmembrane spanning region and an intracellular portion containing a split tyrosine-kinase domain.
VEGF-A binds toVEGFR-1 (Flt-1) andVEGFR-2 (KDR/Flk-1). VEGFR-2 appears to mediate almost all of the known cellular responses to VEGF.[1] 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.[6] 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 bothneuropilins and VEGFRs. This receptor complex has increased VEGF signalling activity inendothelial cells (blood vessels).[7][8] Neuropilins (NRP) arepleiotropic receptors and therefore other molecules may interfere with the signalling of the NRP/VEGFR receptor complexes. For example, Class 3semaphorins compete with VEGF165 for NRP binding and could therefore regulate VEGF-mediatedangiogenesis.[9]
^Fujita N, Imai J, Suzuki T, Yamada M, Ninomiya K, Miyamoto K, et al. (July 2008). "Vascular endothelial growth factor-A is a survival factor for nucleus pulposus cells in the intervertebral disc".Biochemical and Biophysical Research Communications.372 (2):367–72.Bibcode:2008BBRC..372..367F.doi:10.1016/j.bbrc.2008.05.044.PMID18492486.
