Recombinant Human VEGFR1/Flt-1 Fc Chimera Protein

• Reactivity: Hu
• Applications: Bioactivity

Recombinant Human VEGFR1/Flt-1 Fc Chimera Protein 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 ED 50 for this effect is 5-30 ng/mL.
• Source: Spodoptera frugiperda, Sf 21 (baculovirus)-derived human VEGFR1/Flt-1 protein

  Human VEGFR1 (Ser27-His687) Accession # AAC50060

  IEGRMD

  Human IgG 1 (Pro100-Lys330)

  6-His tag

  N-terminus

  C-terminus

• Accession #: AAC50060
• 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: 100 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: 123 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 degreesC as supplied. 3 months, 2 to 8 degreesC under sterile conditions after reconstitution.
• Buffer: Lyophilized from a 0.2 μm filtered solution in MOPS, NaCl and CHAPS with BSA as a carrier protein.
• Purity: >90%, by SDS-PAGE under reducing conditions and visualized by silver stain
• Reconstitution Instructions: Reconstitute at 100 μg/mL in sterile PBS containing at least 0.1% human or bovine serum albumin.

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 Fc Chimera Protein

• 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 up-regulated during hypoxia, and participates in neovascularization and wound healing (1, 2, 15). VEGFR1 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 (321-FL)(42)

Publications using 321-FL

• A Schulz, CC Drost, B Hesse, K Beul, M Brand, GS Di Marco The Soluble Fms-like Tyrosine Kinase-1 Contributes to Structural and Functional Changes in Endothelial Cells in Chronic Kidney Disease International Journal of Molecular Sciences, 2022-12-16;23(24):. 2022-12-16 [PMID: 36555698] (Cell Culture, Human)
• AV Yagolovich, AA Artykov, AA Isakova, YV Vorontsova, DA Dolgikh, MP Kirpichnik, ME Gasparian Optimized Heterologous Expression and Efficient Purification of a New TRAIL-Based Antitumor Fusion Protein SRH-DR5-B with Dual VEGFR2 and DR5 Receptor Specificity International Journal of Molecular Sciences, 2022-05-24;23(11):. 2022-05-24 [PMID: 35682540] (ELISA Capture, Human)
• R Beckmann, K Jensen, S Fenn, J Speck, K Krause, A Meier, M Röth, S Fauser, R Kimbung, DT Logan, M Steegmaier, H Kettenberg DutaFabs are engineered therapeutic Fab fragments that can bind two targets simultaneously Nature Communications, 2021-01-29;12(1):708. 2021-01-29 [PMID: 33514724] (ELISA Capture, Human)
• SB Mamer, A Wittenkell, PI Imoukhuede VEGF-A splice variants bind VEGFRs with differential affinities Sci Rep, 2020-09-02;10(1):14413. 2020-09-02 [PMID: 32879419] (Bioassay, Surface Plasmon Resonance, Human, N/A)
• F Njau, N Shushakova, H Schenk, VC Wulfmeyer, R Bollin, J Menne, H Haller Calcium dobesilate reduces VEGF signaling by interfering with heparan sulfate binding site and protects from vascular complications in diabetic mice PLoS ONE, 2020-01-14;15(1):e0218494. 2020-01-14 [PMID: 31935212] (Bioassay, Human)
• M Verma, Y Shimizu-Mo, Y Asakura, JP Ennen, J Bosco, Z Zhou, GH Fong, S Josiah, D Keefe, A Asakura Inhibition of FLT1 ameliorates muscular dystrophy phenotype by increased vasculature in a mouse model of Duchenne muscular dystrophy PLoS Genet., 2019-12-26;15(12):e1008468. 2019-12-26 [PMID: 31877123] (Surface Plasmon Resonance, Mouse)
• Kristina Haase, Mark R. Gillrie, Cynthia Hajal, Roger D. Kamm Pericytes Contribute to Dysfunction in a Human 3D Model of Placental Microvasculature through VEGF‐Ang‐Tie2 Signaling Advanced Science 2019-12-01 [PMID: 31832308] (Bioassay, Human)
• JA Buczek-Tho, CB Rich, MA Nugent Hypoxia Induced Heparan Sulfate Primes the Extracellular Matrix for Endothelial Cell Recruitment by Facilitating VEGF-Fibronectin Interactions Int J Mol Sci, 2019-10-12;20(20):. 2019-10-12 [PMID: 31614727] (Bioassay, Human)
• M Verma, Y Asakura, BSR Murakonda, T Pengo, C Latroche, B Chazaud, LK McLoon, A Asakura Muscle Satellite Cell Cross-Talk with a Vascular Niche Maintains Quiescence via VEGF and Notch Signaling Cell Stem Cell, 2018-10-04;23(4):530-543.e9. 2018-10-04 [PMID: 30290177] (Bioassay, In Vivo, Mouse)
• KC Wheeler, MK Jena, BS Pradhan, N Nayak, S Das, CD Hsu, DS Wheeler, K Chen, NR Nayak VEGF may contribute to macrophage recruitment and M2 polarization in the decidua PLoS ONE, 2018-01-11;13(1):e0191040. 2018-01-11 [PMID: 29324807] (Bioassay, Human)
• SB Mamer, S Chen, JC Weddell, A Palasz, A Wittenkell, M Kumar, PI Imoukhuede Discovery of High-Affinity PDGF-VEGFR Interactions: Redefining RTK Dynamics Sci Rep, 2017-11-27;7(1):16439. 2017-11-27 [PMID: 29180757] (Surface Plasmon Resonance, Human)
• PI Toivanen, T Nieminen, JP Laakkonen, T Heikura, MU Kaikkonen, S Ylä-Herttu Snake venom VEGF Vammin induces a highly efficient angiogenic response in skeletal muscle via VEGFR-2/NRP specific signaling Sci Rep, 2017-07-17;7(1):5525. 2017-07-17 [PMID: 28717175] (Bioassay, Human)
• J Gibbens, R Morris, T Bowles, SK Spencer, K Wallace Dysregulation of the Fas/FasL system in an experimental animal model of HELLP syndrome Pregnancy Hypertens, 2017-02-24;8(0):26-30. 2017-02-24 [PMID: 28501275] (In Vivo, Rat)
• ME LeBlanc, W Wang, X Chen, NB Caberoy, F Guo, C Shen, Y Ji, H Tian, H Wang, R Chen, W Li Secretogranin III as a disease-associated ligand for antiangiogenic therapy of diabetic retinopathy J. Exp. Med, 2017-03-22;0(0):. 2017-03-22 [PMID: 28330905] (Bioassay)
• Tumor-Derived Factors and Reduced p53 Promote Endothelial Cell Centrosome Over-Duplication PLoS ONE, 2016-12-15;11(12):e0168334. 2016-12-15 [PMID: 27977771] (Bioassay, Human)
• Benjamin Malard Adsorption as a Contributor for Inflammatory Mediators Removal by Different Hemofiltration Membranes: A Pilot Study Artif Organs, 2016-12-02;0(0):. 2016-12-02 [PMID: 27911005] (Hemofiltration Procedure, Human)
• Terrance G Johns Axitinib Has Antiangiogenic and Antitumorigenic Activity in Myxoid Liposarcoma Sarcoma, 2016-10-16;2016(0):3484673. 2016-10-16 [PMID: 27822137] (Bioassay, Human)
• Kyu-Yeon Han, Jin-Hong Chang, Hyun Lee, Dimitri T Azar Proangiogenic Interactions of Vascular Endothelial MMP14 With VEGF Receptor 1 in VEGFA-Mediated Corneal Angiogenesis. Investigative Ophthalmology & Visual Science, 2016-06-01;0(0):1552-5783. 2016-06-01 [PMID: 27327585] (Enzyme Assay, Human)
• Teran M, Nugent M Synergistic Binding of Vascular Endothelial Growth Factor-A and Its Receptors to Heparin Selectively Modulates Complex Affinity. J Biol Chem, 2015-05-15;290(26):16451-62. 2015-05-15 [PMID: 25979342] (Bioassay, Human)
• Maertens L, Erpicum C, Detry B, Blacher S, Lenoir B, Carnet O, Pequeux C, Cataldo D, Lecomte J, Paupert J, Noel A Bone marrow-derived mesenchymal stem cells drive lymphangiogenesis. PLoS ONE, 2014-09-15;9(9):e106976. 2014-09-15 [PMID: 25222747] (Bioassay, Human)
• Yi K, Jung S, Cho G, Seol H, Hong S, Oh M, Kim H Effects of sFlt-1 and alpha 2-macroglobulin on vascular endothelial growth factor-induced endothelin-1 upregulation in human microvascular endothelial cells. Placenta, 2013-09-25;35(1):64-9. 2013-09-25 [PMID: 24231447] (Bioassay, Human)
• Orecchia A, Mettouchi A, Uva P, Simon G, Arcelli D, Avitabile S, Ragone G, Meneguzzi G, Pfenninger K, Zambruno G, Failla C Endothelial cell adhesion to soluble vascular endothelial growth factor receptor-1 triggers a cell dynamic and angiogenic phenotype. FASEB J, 2013-10-30;28(2):692-704. 2013-10-30 [PMID: 24174428] (Bioassay, Human)
• Qi , Jian Hua, Ebrahem , Quteba, Ali , Mariya, Cutler , Alecia, Bell , Brent, Prayson , Nicholas, Sears , Jonathan, Knauper , Vera, Murphy , Gillian, Anand-Apte , Bela Tissue inhibitor of metalloproteinases-3 peptides inhibit angiogenesis and choroidal neovascularization in mice. PLoS ONE, 2013-03-01;8(3):e55667. 2013-03-01 [PMID: 23469166] (ELISA, Human)
• Tabata T, Petitt M, Fang-Hoover J, Rivera J, Nozawa N, Shiboski S, Inoue N, Pereira L Cytomegalovirus impairs cytotrophoblast-induced lymphangiogenesis and vascular remodeling in an in vivo human placentation model. Am J Pathol, 2012-09-07;181(5):1540-59. 2012-09-07 [PMID: 22959908] (Bioassay, Human)
• Schreurs MP, Houston EM, May V, Cipolla MJ The adaptation of the blood-brain barrier to vascular endothelial growth factor and placental growth factor during pregnancy. FASEB J., 2011-09-12;26(1):355-62. 2011-09-12 [PMID: 21911594] (In Vivo, Rat)
• Franco M, Roswall P, Cortez E, Hanahan D, Pietras K Pericytes promote endothelial cell survival through induction of autocrine VEGF-A signaling and Bcl-w expression. Blood, 2011-07-21;118(10):2906-17. 2011-07-21 [PMID: 21778339] (Bioassay, Mouse)
• Goyal A, Pal N, Concannon M, Paul M, Doran M, Poluzzi C, Sekiguchi K, Whitelock JM, Neill T, Iozzo RV Endorepellin, the angiostatic module of perlecan, interacts with both the alpha2beta1 integrin and vascular endothelial growth factor receptor 2 (VEGFR2): a dual receptor antagonism. J. Biol. Chem., 2011-05-19;286(29):25947-62. 2011-05-19 [PMID: 21596751] (Binding Assay, Human)
• Nishiguchi KM, Kataoka K, Kachi S Regulation of pathologic retinal angiogenesis in mice and inhibition of VEGF-VEGFR2 binding by soluble heparan sulfate. PLoS ONE, 2010-10-20;5(10):e13493. 2010-10-20 [PMID: 20975989] (Bioassay, Porcine)
• Lorquet S, Berndt S, Blacher S, Gengoux E, Peulen O, Maquoi E, Noel A, Foidart JM, Munaut C, Pequeux C Soluble forms of VEGF receptor-1 and -2 promote vascular maturation via mural cell recruitment. FASEB J., 2010-05-19;24(10):3782-95. 2010-05-19 [PMID: 20484670] (Bioassay, IHC, Human, Mouse)
• Kishuku M, Nishioka Y, Abe S, Kishi J, Ogino H, Aono Y, Azuma M, Kinoshita K, Batmunkh R, Rentsenhand B, Makino H, Ranjan P, Minakuchi K, Sone S Expression of soluble vascular endothelial growth factor receptor-1 in human monocyte-derived mature dendritic cells contributes to their antiangiogenic property. J. Immunol., 2009-12-15;183(12):8176-85. 2009-12-15 [PMID: 20007583] (Bioassay, Human)
• Rennel ES, Varey AH, Churchill AJ, Wheatley ER, Stewart L, Mather S, Bates DO, Harper SJ VEGF(121)b, a new member of the VEGF(xxx)b family of VEGF-A splice isoforms, inhibits neovascularisation and tumour growth in vivo. Br. J. Cancer, 2009-08-25;101(7):1183-93. 2009-08-25 [PMID: 19707198] (Bioassay, Human)
• Ponticelli S, Marasco D, Tarallo V, Albuquerque RJ, Mitola S, Takeda A, Stassen JM, Presta M, Ambati J, Ruvo M, De Falco S Modulation of angiogenesis by a tetrameric tripeptide that antagonizes vascular endothelial growth factor receptor 1. J. Biol. Chem., 2008-10-15;283(49):34250-9. 2008-10-15 [PMID: 18922791] (Bioassay, Human)
• Lake AC, Vassy R, Di Benedetto M, Lavigne D, Le Visage C, Perret GY, Letourneur D Low molecular weight fucoidan increases VEGF165-induced endothelial cell migration by enhancing VEGF165 binding to VEGFR-2 and NRP1. J. Biol. Chem., 2006-10-06;281(49):37844-52. 2006-10-06 [PMID: 17028197] (Bioassay, Human)
• Red-Horse K, Rivera J, Schanz A, Zhou Y, Winn V, Kapidzic M, Maltepe E, Okazaki K, Kochman R, Vo KC, Giudice L, Erlebacher A, McCune JM, Stoddart CA, Fisher SJ Cytotrophoblast induction of arterial apoptosis and lymphangiogenesis in an in vivo model of human placentation. J. Clin. Invest., 2006-09-21;116(10):2643-52. 2006-09-21 [PMID: 16998586] (Bioassay, Human)
• Narazaki M, Tosato G Ligand-induced internalization selects use of common receptor neuropilin-1 by VEGF165 and semaphorin3A. Blood, 2006-01-19;107(10):3892-901. 2006-01-19 [PMID: 16424390] (ELISA (Standard))
• Xu F, Hazzard TM, Evans A, Charnock-Jones S, Smith S, Stouffer RL Intraovarian actions of anti-angiogenic agents disrupt periovulatory events during the menstrual cycle in monkeys. Contraception, 2005-04-01;71(4):239-48. 2005-04-01 [PMID: 15792643] (In Vivo, Primate - Macaca mulatta (Rhesus Macaque))
• Seo KH, Lee HS, Jung B, Ko HM, Choi JH, Park SJ, Choi IH, Lee HK, Im SY Estrogen enhances angiogenesis through a pathway involving platelet-activating factor-mediated nuclear factor-kappaB activation. Cancer Res., 2004-09-15;64(18):6482-8. 2004-09-15 [PMID: 15374958] (Bioassay, Porcine)
• Kodama I, Sanada M, Yoshiko Y, Tsuda M, Ohama K Estrogen regulates the production of VEGF for osteoclast formation and activity in op/op mice. J. Bone Miner. Res., 2003-12-16;19(2):200-6. 2003-12-16 [PMID: 14969389] (In Vivo, Mouse)
• Caine GJ, Blann AD, Stonelake PS, Ryan P, Lip GY Plasma angiopoietin-1, angiopoietin-2 and Tie-2 in breast and prostate cancer: a comparison with VEGF and Flt-1. Eur. J. Clin. Invest., 2003-10-01;33(10):883-90. 2003-10-01 [PMID: 14511360] (ELISA (Standard))
• Maynard SE, Min JY, Merchan J, Lim KH, Mondal S, Stillman IE, Epstein FH, Karumanchi SA Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J. Clin. Invest., 2003-03-01;111(5):649-58. 2003-03-01 [PMID: 12618519] (Bioassay, Human)
• Argraves WS, Larue AC, Fleming PA, Drake CJ VEGF signaling is required for the assembly but not the maintenance of embryonic blood vessels. Dev. Dyn., 2002-11-01;225(3):298-304. 2002-11-01 [PMID: 12412012] (Bioassay, Avian - Quail, Mouse)
• Arap W, Kolonin MG, Trepel M, Lahdenranta J, Cardo-Vila M, Giordano RJ, Mintz PJ, Ardelt PU, Yao VJ, Vidal CI, Chen L, Flamm A, Valtanen H, Weavind LM, Hicks ME, Pollock RE, Botz GH, Bucana CD, Koivunen E, Cahill D, Troncoso P, Baggerly KA, Pentz RD, Do KA, Logothetis CJ, Pasqualini R Steps toward mapping the human vasculature by phage display. Nat. Med., 2002-02-01;8(2):121-7. 2002-02-01 [PMID: 11821895] (Binding Assay, Human)

Bioinformatics

• Gene Symbol: FLT1
• Uniprot:
  • AAC50060()