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 # P35969IEGRMDP Mouse IgG2A
(Glu98-Lys330)N-terminus C-terminus Accession #
N-terminal Sequence
AnalysisSer27
Structure / Form
Disulfide-linked homodimer
Predicted Molecular Mass
109.6 kDa (monomer)
SDS-PAGE
130-150 kDa, reducing conditions
7756-FL |
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Formulation Lyophilized from a 0.2 μm filtered solution in PBS. | ||
Reconstitution Reconstitute at 100 μg/mL in PBS. | ||
Shipping The product is shipped at ambient temperature. Upon receipt, store it immediately at the temperature recommended below. | ||
Stability & Storage: Use a manual defrost freezer and avoid repeated freeze-thaw cycles.
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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:
Otrock, Z.K. et al. (2007) Blood Cells Mol. Dis. 38:258.
Peters, K.G. et al. (1993) Proc. Natl. Acad. Sci. USA 90:8915.
Murakami, M. et al. (2008) Arterioscler. Thromb. Vasc. Biol. 28:658.
Al-Ani, B. et al. (2010) Hypertension 55:689.
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He, Y. et al. (1999) Molecular Endocrinology 13:537.
Cai, J. et al. (2012) EMBO Mol. Med. 4:980.
Kendall, R.L. and K.A. Thomas (1993) Proc. Natl. Acad. Sci. USA 90:10705.
Sawano, A. et al. (1996) Cell Growth Differ. 7:213.
Barleon, B. et al. (1997) J. Biol. Chem. 272:10382.
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Mac Gabhann, F. and A.S. Popel (2007) Biophys. Chem. 128:125.
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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
