KDRVEGFR2

KDRVEGFR2, commonly referred to as VEGFR-2 or Flk-1, is a receptor tyrosine kinase that belongs to the vascular endothelial growth factor receptor family. In humans it is encoded by the KDR gene and is expressed primarily on vascular endothelial cells, with detection also in certain hematopoietic progenitors and other cell types under specific conditions. The receptor plays a central role in angiogenesis and vascular homeostasis.

The protein has an extracellular domain composed of multiple immunoglobulin-like motifs, a single transmembrane helix, and an intracellular tyrosine kinase domain. The extracellular region mediates ligand binding, while the intracellular domain undergoes autophosphorylation upon receptor dimerization. VEGFR-2 is activated mainly by VEGF-A, the principal ligand, with additional interactions from other VEGF family members under certain contexts.

Upon ligand binding and activation, VEGFR-2 initiates multiple signaling cascades, including the PI3K-Akt pathway for endothelial survival, the PLCγ pathway influencing calcium signaling, and the Ras-MAPK pathway promoting proliferation and migration. This signaling drives endothelial cell proliferation, migration, vascular permeability, and new blood vessel formation.

VEGFR-2 is essential for normal embryonic vascular development and contributes to physiological angiogenesis in wound healing and tissue regeneration. Dysregulation of VEGFR-2 signaling is linked to pathological angiogenesis in cancers, diabetic retinopathy, and inflammatory diseases. Clinically, the axis is a major target for anti-angiogenic therapy: monoclonal antibodies such as ramucirumab target VEGFR-2, and small-molecule tyrosine kinase inhibitors (e.g., sunitinib, sorafenib, axitinib, pazopanib) inhibit the receptor's kinase activity. Soluble VEGFR-2 isoforms can act as decoy receptors to modulate VEGF availability.