VEGF R1 (vascular endothelial growth factor receptor 1), also called Flt‑1 (Fms‑like tyrosine kinase), is a 180 kDa type I transmembrane glycoprotein in the class III subfamily of receptor tyrosine kinases (RTKs) (1, 2). While family members VEGF R1, VEGF R2/KDR/Flk‑1 and VEGF R3/Flt‑4 are all mainly expressed on endothelial cells and play central roles in vasculogenesis, angiogenesis, and lymphangiogenesis, only VEGF R1 is expressed on macrophages, and mainly plays inhibitory roles (1‑3). VEGF R1 expression is also reported on osteoblasts, placental trophoblasts, renal mesangial cells, and some hematopoietic stem cells (1, 2). Like other class III RTKs, mouse VEGF R1 contains a signal peptide (aa 1‑22), an extracellular domain (ECD aa 23‑759) with seven Ig‑like repeats, a transmembrane domain (aa 760‑781) and a cytoplasmic region (aa 782‑1333) with a tyrosine kinase domain and several autocatalytic phosphotyrosine sites. Mouse VEGF R1 ECD shares 91% aa sequence identity with rat and 76‑79% with human, equine, canine and porcine VEGF R1. Soluble forms of the VEGF R1 ECD are produced by alternative splicing, and may also be shed during regulated intracellular proteolysis (4‑10). Both soluble and transmembrane forms can inhibit angiogenesis by binding and sequestering its ligands, VEGF (VEGF‑A), VEGF‑B or PlGF (6‑11). VEGF R1 dimerizes upon ligand binding, which can include heterodimerization with VEGF R2 that modifies VEGF R2‑mediated endothelial proliferation and vessel branching (8, 11, 12). VEGF R1 binds VEGF with higher affinity than does VEGF R2, but shows weaker kinase activity (9, 13). Both PlGF and VEGF induce phosphorylation of transmembrane VEGF R1 (5, 9, 13). While deletion of mouse VEGF R1 is lethal due to overgrowth and disorganization of the vasculature, kinase‑inactive mutants are viable (13, 14). VEGF R1 is up‑regulated during hypoxia, and participates in neovascularization and wound healing (1, 2, 15). VEGF R1 engagement on monocyte/macrophage lineage cells enhances their migration, and release of growth factors and cytokines (1, 3, 13, 16). Lymphangiogenesis, angiogenesis, and growth‑promoting effects of VEGF R1 are thought to result from enhanced migration of macrophages from the bone marrow to tumors and tissues where they recruit endothelial progenitors (3, 16). Circulating levels of VEGF R1 increase during pregnancy and are further elevated in preeclampsia (4, 6, 17).