VEGFR1FLT1

VEGFR1, also known as FLT1 or Flt-1, is a receptor tyrosine kinase in the vascular endothelial growth factor (VEGF) receptor family. It binds several VEGF ligands, including VEGF-A, VEGF-B, and placental growth factor (PlGF). The FLT1 gene is expressed mainly in endothelial cells and plays a complex role in angiogenesis and vascular homeostasis.

VEGFR1 is a single-pass transmembrane protein with an extracellular ligand-binding region containing immunoglobulin-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Alternative splicing produces a soluble form, sFLT-1, which lacks the membrane-spanning and kinase regions and can circulate as a decoy receptor, sequestering VEGF ligands.

Ligand binding activates the receptor’s intracellular signaling, though VEGFR1 signaling is generally weaker than that of VEGFR2 (VEGFR-2). VEGFR1 participates in modulating angiogenesis and vascular permeability by regulating VEGF availability and cross-talk with VEGFR2. Downstream pathways linked to VEGFR1 include PI3K/AKT and MAPK/ERK signaling, contributing to endothelial cell survival and migration in certain contexts.

FLT1 expression is developmentally regulated and responsive to cues such as hypoxia and vascular demand. The balance between VEGFR1 and VEGFR2 signaling influences the angiogenic outcome in tissues.

Clinically, VEGFR1 contributes to pathological angiogenesis in diseases such as cancer, where anti-angiogenic strategies may target VEGF receptors. The soluble FLT-1 isoform is a key factor in preeclampsia, where elevated sFLT-1 reduces circulating VEGF availability and disrupts placental angiogenesis. Therapeutic approaches include drugs that inhibit VEGF signaling, indirectly affecting VEGFR1 activity.