Vascular endothelial growth factor receptor signaling (VEGF/VEGFR signaling)

Vascular endothelial growth factor receptor signaling is a central pathway in the regulation of vascular development and homeostasis. VEGF ligands (VEGF-A, -C, -D, and placental growth factor) bind to VEGFR-1, VEGFR-2, and VEGFR-3, which are transmembrane receptor tyrosine kinases expressed primarily on endothelial cells. Ligand binding induces receptor dimerization and autophosphorylation, activating several downstream pathways—Ras/MAPK (cell proliferation), PI3K/AKT (cell survival), PLCγ (vascular permeability), and FAK/paxillin (cell migration/cytoskeletal rearrangement). The major physiological output is the formation of new blood vessels (angiogenesis), increased vascular permeability, and lymphangiogenesis (VEGFR-3). Dysregulation leads to pathological angiogenesis in cancer, retinal disease, and cardiovascular disorders. Multiple approved drugs inhibit the VEGF/VEGFR signaling axis to block tumor angiogenesis, but use is limited by safety concerns such as hypertension, impaired wound healing, and bleeding risk. If you need information on a specific VEGF receptor (e.g. VEGFR-2/KDR), this pathway can be mapped directly to “Vascular endothelial growth factor receptor 2” as the most prominent therapeutic target in the axis.

Other names

VEGF signalingVEGFR pathwayAngiogenesis pathwayVascular endothelial growth factor pathwayVEGFA-VEGFR2 pathway

Ligand binding inhibition (antibodies/decoy receptors prevent VEGF from reaching VEGFR); Tyrosine kinase inhibition (small molecules block VEGFR kinase activity); Blockade of downstream signaling pathways (e.g. Ras/MAPK, PI3K/AKT, PLCγ)