Vascular endothelial growth factor receptor 2 - Vascular endothelial growth factor signaling complex (VEGFR-2 - VEGF complex)

The Vascular endothelial growth factor receptor 2 (VEGFR-2) – Vascular endothelial growth factor (VEGF) signaling complex is a primary driver of angiogenesis, the process of new blood vessel formation from pre-existing vasculature (UniProt P35968, P15692). This complex is formed when VEGF-A ligands bind to the extracellular domain of VEGFR-2, a receptor tyrosine kinase, leading to receptor dimerization and autophosphorylation of its intracellular domain (PubMed: 23673320). This activation triggers multiple downstream signaling pathways, including the MAPK/ERK and PI3K/AKT cascades, which promote endothelial cell proliferation, migration, and survival (StatPearls: Angiogenesis Inhibitors). In pathological states, particularly in solid tumors, over-activation of this complex facilitates tumor neovascularization, providing the nutrients and oxygen necessary for tumor growth and metastasis (PubMed: 15660110). Consequently, this signaling axis is a major therapeutic target in oncology and ophthalmology, with drugs designed to either neutralize the VEGF ligand or inhibit the VEGFR-2 kinase activity to starve tumors of their blood supply or reduce pathological vascular leakage (PubMed: 28338604).

Other names

KDR-VEGFA complexFLK1-VEGF complexVEGF/VEGFR2 signaling axisVascular endothelial growth factor receptor 2 - Vascular endothelial growth factor A complex

Inhibition of the signaling complex occurs through two primary modalities: monoclonal antibodies (e.g., bevacizumab) or decoy receptors (e.g., aflibercept) that sequester the VEGF ligand, and small molecule tyrosine kinase inhibitors (e.g., sunitinib) that block the intracellular catalytic activity of VEGFR-2, thereby preventing downstream signal transduction (PubMed: 28338604).