Recombinant Human VEGFR1/Flt-1 (aa 27-328) Fc Chimera, CF

• Reactivity: Hu
• Applications: Bioactivity
• Format: Carrier-Free

Recombinant Human VEGFR1/Flt-1 (aa 27-328) Fc Chimera, CF Summary

• Details of Functionality: Measured by its ability to inhibit the VEGF-dependent proliferation of HUVEC human umbilical vein endothelial cells. Conn, G. et al. (1990) Proc. Natl. Acad. Sci. USA 87:1323. The ED₅₀ for this effect is 3-15 ng/mL.
• Source: Mouse myeloma cell line, NS0-derived human VEGFR1/Flt-1 protein
  

  Human VEGFR1 (Ser27-lle328) Accession #P17948	IEGRMD	Human IgG1 (Pro100-Lys330)
  N-terminus		C-terminus

• Accession #: P17948
• N-terminal Sequence: Ser27
• Structure / Form: Disulfide-linked homodimer
• Protein/Peptide Type: Recombinant Proteins
• Gene: FLT1
• Purity: >90%, by SDS-PAGE under reducing conditions and visualized by silver stain.
• Endotoxin Note: <0.10 EU per 1 μg of the protein by the LAL method.

Applications/Dilutions

• Dilutions:
  • Bioactivity
• Theoretical MW: 60.7 kDa (monomer).
  Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors.
• SDS-PAGE: 75-85 kDa, reducing conditions

Packaging, Storage & Formulations

• Storage: Use a manual defrost freezer and avoid repeated freeze-thaw cycles.
  • 12 months from date of receipt, -20 to -70 °C as supplied.
  • 1 month, 2 to 8 °C under sterile conditions after reconstitution.
  • 3 months, -20 to -70 °C under sterile conditions after reconstitution.
• Buffer: Lyophilized from a 0.2 μm filtered solution in PBS.
• Purity: >90%, by SDS-PAGE under reducing conditions and visualized by silver stain.
• Reconstitution Instructions: Reconstitute at 100 μg/mL in sterile PBS.

Notes

This product is produced by and ships from R&D Systems, Inc., a Bio-Techne brand.

Alternate Names for Recombinant Human VEGFR1/Flt-1 (aa 27-328) Fc Chimera, CF

• 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

Background

VEGFR1 (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 VEGFR1, VEGFR2/KDR/Flk-1 and VEGFR3/Flt-4 are all mainly expressed on endothelial cells and play central roles in vasculogenesis, angiogenesis, and lymphangiogenesis, only VEGFR1 is expressed on macrophages, and mainly plays inhibitory roles (1-3). VEGFR1 expression is also reported on osteoblasts, placental trophoblasts, renal mesangial cells, and some hematopoietic stem cells (1, 2). Like other class III RTKs, human VEGFR1 contains a signal peptide (aa 1-22), an extracellular domain (ECD aa 27-758) with seven Ig-like repeats, a transmembrane domain (aa 759-780) and a cytoplasmic region (aa 781-1338) with a tyrosine kinase domain and several autocatalytic phosphotyrosine sites. Human VEGFR1 ECD shares 78%, 78%, 84%, 87%, and 90% aa sequence identity with mouse, rat, porcine, canine and equine VEGFR1, respectively. Soluble forms of the VEGFR1 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). VEGFR1 dimerizes upon ligand binding, which can include heterodimerization with VEGFR2 that modifies VEGFR2-mediated endothelial proliferation and vessel branching (8, 11, 12). VEGFR1 binds VEGF with higher affinity than does VEGFR2, but shows weaker kinase activity (9, 13). Both PlGF and VEGF induce autophosphorylation of transmembrane VEGFR1 (5, 9, 13). While deletion of mouse VEGFR1 is lethal due to overgrowth and disorganization of the vasculature, kinase-inactive mutants are viable (13, 14). VEGFR1 is upregulated 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 VEGFR1 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 VEGFR1 increase during pregnancy and are further elevated in preeclampsia (4, 6, 17).

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.

Publications for VEGFR1/Flt-1 (3516-FL)(1)

Publication using 3516-FL

• Tatsuya Miyake, Keiichi Kumasawa, Noriko Sato, Tsuyoshi Takiuchi, Hitomi Nakamura, Tadashi Kimura Soluble VEGF receptor 1 (sFLT1) induces non-apoptotic death in ovarian and colorectal cancer cells. Scientific Reports, 2016-04-22;0(0):2045-2322. 2016-04-22 [PMID: 27103202] (Bioassay, Human)

Bioinformatics

• Gene Symbol: FLT1
• Uniprot:
  • P17948()