• Purity

  >95%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.

• Endotoxin Level

  <0.10 EU per 1 μg of the protein by the LAL method.  

• Activity

  Measured by its ability to inhibit the VEGF-dependent proliferation of HUVEC human umbilical vein endothelial cells. The ED    ₅₀ for this effect is 5-30 ng/mL.

• Source

  Mouse myeloma cell line, NS0-derived

  Mouse VEGF R1 (Ser27-Glu759) Accession # P35969	IEGRMDP	Mouse IgG2A (Glu98-Lys330)
  N-terminus		C-terminus

• Accession #

• N-terminal Sequence    
  Analysis

  Ser27

• Structure / Form

  Disulfide-linked homodimer

• Predicted Molecular Mass

  109.6 kDa (monomer)

• SDS-PAGE

  130-150 kDa, reducing conditions

Background: VEGF R1/Flt-1

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).

• References:

1. Otrock, Z.K. et al. (2007) Blood Cells Mol. Dis. 38:258.

2. Peters, K.G. et al. (1993) Proc. Natl. Acad. Sci. USA 90:8915.

3. Murakami, M. et al. (2008) Arterioscler. Thromb. Vasc. Biol. 28:658.

4. Al-Ani, B. et al. (2010) Hypertension 55:689.

5. Rahimi, N. et al. (2009) Cancer Res. 69:2607.

6. He, Y. et al. (1999) Molecular Endocrinology 13:537.

7. Cai, J. et al. (2012) EMBO Mol. Med. 4:980.

8. Kendall, R.L. and K.A. Thomas (1993) Proc. Natl. Acad. Sci. USA 90:10705.

9. Sawano, A. et al. (1996) Cell Growth Differ. 7:213.

10. Barleon, B. et al. (1997) J. Biol. Chem. 272:10382.

11. Kappas, N.C. et al. (2008) J. Cell Biol. 181:847.

12. Mac Gabhann, F. and A.S. Popel (2007) Biophys. Chem. 128:125.

13. Hiratsuka, S. et al. (1998) Proc. Natl. Acad. Sci. USA 95:9349.

14. Fong, G.H. et al. (1995) Nature 376:66.

15. Nishi, J. et al. (2008) Circ. Res. 103:261.

16. Muramatsu, M. et al. (2010) Cancer Res. 70:8211.

17. Levine, R.J. et al. (2004) N. Engl. J. Med. 350:672.

• Long Name:

  Vascular Endothelial Growth Factor Receptor 1

• Entrez Gene IDs:

  2321 (Human); 14254 (Mouse)

• Alternate Names:

  EC 2.7.10; EC 2.7.10.1; FLT; FLT1; Flt-1; Fms-like tyrosine kinase 1; fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascularpermeability factor receptor); FRT; Tyrosine-protein kinase FRT; Tyrosine-protein kinase receptor FLT; vascular endothelial growth factor receptor 1; Vascular permeability factor receptor; VEGF R1; VEGFR1; VEGFR-1