Vascular endothelial growth factor receptor 1 and vascular endothelial growth factor receptor 2 (VEGFR-1 (also known as Flt-1), VEGFR-2 (also known as KDR or Flk-1))

Vascular endothelial growth factor receptor 1 (VEGFR-1/Flt-1) and vascular endothelial growth factor receptor 2 (VEGFR-2/KDR/Flk-1) are structurally homologous, single-pass transmembrane receptors on endothelial cells, critical for the detection and transduction of VEGF family ligands. Both receptors possess an extracellular domain with seven immunoglobulin-like motifs, a transmembrane region, and an intracellular region containing a split tyrosine kinase domain. VEGFR-2 is the principal signal transducer for angiogenic stimuli and regulates endothelial proliferation, migration, and permeability, whereas VEGFR-1 is functionally a kinase-impaired decoy that limits excessive VEGFR-2 activity by sequestering VEGF-A. Activation of VEGFR-2 by VEGF-A, VEGF-C, or VEGF-D induces phosphorylation of several key tyrosine residues and triggers downstream signaling pathways central in vascular development, cancer progression, and neovascular diseases. Both receptors are validated drug targets, with several approved inhibitors in oncology and ophthalmology, though safety profiles require monitoring due to vascular-related side effects.

Other names

Flt-1FLT1KDRFlk-1

Small molecule kinase inhibitors block ATP binding at the kinase domain, inhibiting signal transduction. Monoclonal antibodies bind and prevent VEGF/receptor interaction or induce receptor internalization.