Genomes and Genes
Gene Symbol: Flt1
Description: FMS-like tyrosine kinase 1
Alias: AI323757, Flt-1, VEGFR-1, VEGFR1, sFlt1, vascular endothelial growth factor receptor 1, embryonic receptor kinase 2, tyrosine-protein kinase receptor FLT, vascular permeability factor receptor
- Zelzer E, McLean W, Ng Y, Fukai N, Reginato A, Lovejoy S, et al. Skeletal defects in VEGF(120/120) mice reveal multiple roles for VEGF in skeletogenesis. Development. 2002;129:1893-904 pubmed..We also describe new in vivo evidence for a possible role of VEGF in chondrocyte maturation, and document that VEGF has a direct role in regulating osteoblastic activity based on in vivo evidence and organ culture experiments. ..
- Breier G, Clauss M, Risau W. Coordinate expression of vascular endothelial growth factor receptor-1 (flt-1) and its ligand suggests a paracrine regulation of murine vascular development. Dev Dyn. 1995;204:228-39 pubmed..To evaluate the role of VEGF receptor-1/flt-1 (VEGFR1/flt-1) in the development of the vascular system, we have characterized the murine homolog of the human flt-1 gene ..
- Jin J, Sison K, Li C, Tian R, Wnuk M, Sung H, et al. Soluble FLT1 binds lipid microdomains in podocytes to control cell morphology and glomerular barrier function. Cell. 2012;151:384-99 pubmed publisher..Unlike FLK1/KDR, the role of FLT1 has remained elusive. FLT1 is produced as soluble (sFLT1) and full-length isoforms. Here, we show that pericytes from multiple tissues produce sFLT1...
- Murakami M, Zheng Y, Hirashima M, Suda T, Morita Y, Ooehara J, et al. VEGFR1 tyrosine kinase signaling promotes lymphangiogenesis as well as angiogenesis indirectly via macrophage recruitment. Arterioscler Thromb Vasc Biol. 2008;28:658-64 pubmed publisher..However, the mechanism by which VEGFR1 is involved in lymphangiogenesis remains unclear...
- Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 1996;380:435-9 pubmed
- Ambati B, Nozaki M, Singh N, Takeda A, Jani P, Suthar T, et al. Corneal avascularity is due to soluble VEGF receptor-1. Nature. 2006;443:993-7 pubmed
- Kubota Y, Takubo K, Shimizu T, Ohno H, Kishi K, Shibuya M, et al. M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis. J Exp Med. 2009;206:1089-102 pubmed publisher..Continuous M-CSF inhibition did not affect healthy vascular and lymphatic systems outside tumors. These results suggest that M-CSF-targeted therapy is an ideal strategy for treating ocular neovascular diseases and cancer. ..
- Kraut N, Snider L, Chen C, Tapscott S, Groudine M. Requirement of the mouse I-mfa gene for placental development and skeletal patterning. EMBO J. 1998;17:6276-88 pubmed..Our results indicate that I-mfa plays an important role in trophoblast and chondrogenic differentiation by negatively regulating a subset of lineage-restricted bHLH proteins. ..
- Meyer R, Mohammadi M, Rahimi N. A single amino acid substitution in the activation loop defines the decoy characteristic of VEGFR-1/FLT-1. J Biol Chem. 2006;281:867-75 pubmed
- Suchting S, Freitas C, Le Noble F, Benedito R, Breant C, Duarte A, et al. The Notch ligand Delta-like 4 negatively regulates endothelial tip cell formation and vessel branching. Proc Natl Acad Sci U S A. 2007;104:3225-30 pubmed..Taken together, these data reveal Dll4 as a negative regulator of vascular sprouting and vessel branching that is required for normal vascular network formation during development. ..
- Roberts D, Kearney J, Johnson J, Rosenberg M, Kumar R, Bautch V. The vascular endothelial growth factor (VEGF) receptor Flt-1 (VEGFR-1) modulates Flk-1 (VEGFR-2) signaling during blood vessel formation. Am J Pathol. 2004;164:1531-5 pubmed
- Kleinman M, Yamada K, Takeda A, Chandrasekaran V, Nozaki M, Baffi J, et al. Sequence- and target-independent angiogenesis suppression by siRNA via TLR3. Nature. 2008;452:591-7 pubmed publisher..trials of small interfering RNA (siRNA) targeting vascular endothelial growth factor-A (VEGFA) or its receptor VEGFR1 (also called FLT1), in patients with blinding choroidal neovascularization (CNV) from age-related macular ..
- Ho V, Duan L, Cronin C, Liang B, Fong G. Elevated vascular endothelial growth factor receptor-2 abundance contributes to increased angiogenesis in vascular endothelial growth factor receptor-1-deficient mice. Circulation. 2012;126:741-52 pubmed publisher..Upregulation of VEGFR-2 abundance at the protein level contributes in part to increased angiogenesis in VEGFR-1-deficient mice. ..
- Otomo H, Sakai A, Uchida S, Tanaka S, Watanuki M, Moriwaki S, et al. Flt-1 tyrosine kinase-deficient homozygous mice result in decreased trabecular bone volume with reduced osteogenic potential. Bone. 2007;40:1494-501 pubmed..Flt-1) signaling in bone dynamics, we examined C57BL/6J mice, aged 6, 9 and 16 weeks, with disruption of the flt1 tyrosine kinase domain gene (flt1(TK-/-)) and compared with age-matched wild-type (flt1(TK+/+)) mice...
- Zelzer E, Glotzer D, Hartmann C, Thomas D, Fukai N, Soker S, et al. Tissue specific regulation of VEGF expression during bone development requires Cbfa1/Runx2. Mech Dev. 2001;106:97-106 pubmed..The results demonstrate that Cbfa1 is a necessary component of a tissue specific genetic program that regulates VEGF during endochondral bone formation. ..
- Kerber M, Reiss Y, Wickersheim A, Jugold M, Kiessling F, Heil M, et al. Flt-1 signaling in macrophages promotes glioma growth in vivo. Cancer Res. 2008;68:7342-51 pubmed publisher..Collectively, these results suggest that Flt-1 signaling in myeloid cells is essential to amplify the angiogenic response and to promote glioma growth. ..
- LeCouter J, Moritz D, Li B, Phillips G, Liang X, Gerber H, et al. Angiogenesis-independent endothelial protection of liver: role of VEGFR-1. Science. 2003;299:890-3 pubmed..Thus, VEGFR-1 agonists may have therapeutic potential for preservation of organ function in certain liver disorders. ..
- French W, Creemers E, Tallquist M. Platelet-derived growth factor receptors direct vascular development independent of vascular smooth muscle cell function. Mol Cell Biol. 2008;28:5646-57 pubmed publisher..Together, these data demonstrate that PDGF receptors cooperate in the yolk sac mesothelium to direct blood vessel maturation and suggest that these effects are independent of their role in VSMC development...
- Kearney J, Ambler C, Monaco K, Johnson N, Rapoport R, Bautch V. Vascular endothelial growth factor receptor Flt-1 negatively regulates developmental blood vessel formation by modulating endothelial cell division. Blood. 2002;99:2397-407 pubmed..Taken together, these data show that flt-1 normally modulates vascular growth by controlling the rate of endothelial cell division both in vitro and in vivo. ..
- Breier G, Albrecht U, Sterrer S, Risau W. Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development. 1992;114:521-32 pubmed..g. in choroid plexus and in kidney glomeruli. The data are consistent with a role of VEGF as a multifunctional regulator of endothelial cell growth and differentiation. ..
- Sato T, Amano H, Ito Y, Eshima K, Minamino T, Ae T, et al. Vascular endothelial growth factor receptor 1 signaling facilitates gastric ulcer healing and angiogenesis through the upregulation of epidermal growth factor expression on VEGFR1+CXCR4 + cells recruited from bone marrow. J Gastroenterol. 2014;49:455-69 pubmed publisherAngiogenesis is essential for gastric ulcer healing. Recent results suggest that vascular endothelial growth factor receptor 1 (VEGFR1), which binds to VEGF, promotes angiogenesis...
- Regan C, Li W, Boucher D, Spatz S, Su M, Kuida K. Erk5 null mice display multiple extraembryonic vascular and embryonic cardiovascular defects. Proc Natl Acad Sci U S A. 2002;99:9248-53 pubmed..Moreover, the inability of Erk5-deficient mice to form a complex vasculature suggests that Erk5 may play an important role in controlling angiogenesis. ..
- Koga J, Matoba T, Egashira K, Kubo M, Miyagawa M, Iwata E, et al. Soluble Flt-1 gene transfer ameliorates neointima formation after wire injury in flt-1 tyrosine kinase-deficient mice. Arterioscler Thromb Vasc Biol. 2009;29:458-64 pubmed publisher..These results suggest that endogenous VEGF accelerates neointima formation through flk-1 by regulating MCP-1 expression in VSMCs and macrophage-mediated inflammation in injured vascular wall in murine model of wire injury. ..
- Niida S, Kondo T, Hiratsuka S, Hayashi S, Amizuka N, Noda T, et al. VEGF receptor 1 signaling is essential for osteoclast development and bone marrow formation in colony-stimulating factor 1-deficient mice. Proc Natl Acad Sci U S A. 2005;102:14016-21 pubmed..factor 1 (CSF-1) and VEGF signals interact in osteoclastogenesis, we introduced a VEGFR-1 signaling deficiency (Flt1(TK)-/-) into op/op mice...
- Gerber H, Condorelli F, Park J, Ferrara N. Differential transcriptional regulation of the two vascular endothelial growth factor receptor genes. Flt-1, but not Flk-1/KDR, is up-regulated by hypoxia. J Biol Chem. 1997;272:23659-67 pubmed..These findings indicate that, unlike the KDR/Flk-1 gene, the Flt-1 receptor gene is directly up-regulated by hypoxia via a hypoxia-inducible enhancer element located at positions -976 to -937 of the Flt-1 promoter. ..
- Krueger J, Liu D, Scholz K, Zimmer A, Shi Y, Klein C, et al. Flt1 acts as a negative regulator of tip cell formation and branching morphogenesis in the zebrafish embryo. Development. 2011;138:2111-20 pubmed publisher..Zebrafish embryos expressed soluble Flt1 (sFlt1) and membrane-bound Flt1 (mFlt1)...
- Erskine L, Reijntjes S, Pratt T, Denti L, Schwarz Q, Vieira J, et al. VEGF signaling through neuropilin 1 guides commissural axon crossing at the optic chiasm. Neuron. 2011;70:951-65 pubmed publisher..These findings have identified a permissive midline signal for axons at the chiasm midline and provide in vivo evidence that VEGF-A is an essential axon guidance cue. ..
- Li F, Hagaman J, Kim H, Maeda N, Jennette J, Faber J, et al. eNOS deficiency acts through endothelin to aggravate sFlt-1-induced pre-eclampsia-like phenotype. J Am Soc Nephrol. 2012;23:652-60 pubmed publisherExcess soluble fms-like tyrosine kinase 1 (sFlt-1) of vascular endothelial growth factor receptor 1 secreted from the placenta causes pre-eclampsia-like features by antagonizing vascular endothelial growth factor signaling, which can ..
- Hiratsuka S, Nakao K, Nakamura K, Katsuki M, Maru Y, Shibuya M. Membrane fixation of vascular endothelial growth factor receptor 1 ligand-binding domain is important for vasculogenesis and angiogenesis in mice. Mol Cell Biol. 2005;25:346-54 pubmed..endothelial growth factor (VEGF) regulates vasculogenesis and angiogenesis by using two tyrosine kinase receptors, VEGFR1 and VEGFR2. VEGFR1 null mutant mice die on embryonic day 8.5 (E8.5) to E9...
- Sakurai Y, Ohgimoto K, Kataoka Y, Yoshida N, Shibuya M. Essential role of Flk-1 (VEGF receptor 2) tyrosine residue 1173 in vasculogenesis in mice. Proc Natl Acad Sci U S A. 2005;102:1076-81 pubmed..In contrast, Flk-1(1212F) homozygous mice were viable and fertile. These results suggest that the signaling via Y1173 of Flk-1 is essential for endothelial and hematopoietic development during embryogenesis. ..
- Shalaby F, Rossant J, Yamaguchi T, Gertsenstein M, Wu X, Breitman M, et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature. 1995;376:62-6 pubmed..These results indicate that Flk-1 is essential for yolk-sac blood-island formation and vasculogenesis in the mouse embryo. ..
- Hiratsuka S, Minowa O, Kuno J, Noda T, Shibuya M. Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc Natl Acad Sci U S A. 1998;95:9349-54 pubmed..These results indicate that Flt-1 without tyrosine kinase domain is sufficient to allow embryonic development with normal angiogenesis, and that a receptor tyrosine kinase plays a main biological role as a ligand-binding molecule. ..
- Marti H, Risau W. Systemic hypoxia changes the organ-specific distribution of vascular endothelial growth factor and its receptors. Proc Natl Acad Sci U S A. 1998;95:15809-14 pubmed..In these tissues, up- or down-regulation of VEGF and VEGFR-1 during hypoxia may influence their oxygenation after angiogenesis or modulate vascular permeability. ..
- Ohkubo H, Ito Y, Minamino T, Mishima T, Hirata M, Hosono K, et al. Leukotriene B4 type-1 receptor signaling promotes liver repair after hepatic ischemia/reperfusion injury through the enhancement of macrophage recruitment. FASEB J. 2013;27:3132-43 pubmed publisher..expression of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and VEGF receptor 1 (VEGFR1)...
- Fischer C, Jonckx B, Mazzone M, Zacchigna S, Loges S, Pattarini L, et al. Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell. 2007;131:463-75 pubmed..The efficacy and safety of alphaPlGF, its pleiotropic and complementary mechanism to VEGF(R)Is, and the negligible induction of an angiogenic rescue program suggest that alphaPlGF may constitute a novel approach for cancer treatment. ..
- Fong G, Rossant J, Gertsenstein M, Breitman M. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature. 1995;376:66-70 pubmed..We suggest that the Flt-1 signalling pathway may regulate normal endothelial cell-cell or cell-matrix interactions during vascular development. ..
- Hattori K, Heissig B, Wu Y, Dias S, Tejada R, Ferris B, et al. Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat Med. 2002;8:841-9 pubmed..Here, we report that functional vascular endothelial growth factor receptor-1 (VEGFR1) is expressed on human CD34(+) and mouse Lin(-)Sca-1(+)c-Kit(+) BM-repopulating stem cells, conveying signals for ..
- Kearney J, Kappas N, Ellerstrom C, DiPaola F, Bautch V. The VEGF receptor flt-1 (VEGFR-1) is a positive modulator of vascular sprout formation and branching morphogenesis. Blood. 2004;103:4527-35 pubmed..Thus precise levels of bioactive VEGF-A and perhaps spatial localization of the VEGF signal are likely modulated by flt-1 to ensure proper sprout formation during blood vessel formation. ..
- Fong G, Zhang L, Bryce D, Peng J. Increased hemangioblast commitment, not vascular disorganization, is the primary defect in flt-1 knock-out mice. Development. 1999;126:3015-25 pubmed..These results define the primary defect in flt-1(-/-) embryos at the cellular level and demonstrate the importance of population density of progenitor cells in pattern formation. ..
- Bergmann A, Ahmad S, Cudmore M, Gruber A, Wittschen P, Lindenmaier W, et al. Reduction of circulating soluble Flt-1 alleviates preeclampsia-like symptoms in a mouse model. J Cell Mol Med. 2010;14:1857-67 pubmed publisher..This demonstrates that below a critical threshold sFlt-1 fails to elicit damage to the fenestrated endothelium and that co-expression of VEGF is able to rescue effects mediated by sFlt-1 overexpression. ..
- Maes C, Stockmans I, Moermans K, Van Looveren R, Smets N, Carmeliet P, et al. Soluble VEGF isoforms are essential for establishing epiphyseal vascularization and regulating chondrocyte development and survival. J Clin Invest. 2004;113:188-99 pubmed..These findings indicate that the insoluble VEGF(188) isoform is insufficient for establishing epiphyseal vascularization and regulating cartilage development during endochondral bone formation...
- Guillemot F, Nagy A, Auerbach A, Rossant J, Joyner A. Essential role of Mash-2 in extraembryonic development. Nature. 1994;371:333-6 pubmed..Mash-2 is the first transcription factor shown to play a critical part in the development of the mammalian trophoblast lineage. ..
- He Y, Smith S, Day K, Clark D, Licence D, Charnock Jones D. Alternative splicing of vascular endothelial growth factor (VEGF)-R1 (FLT-1) pre-mRNA is important for the regulation of VEGF activity. Mol Endocrinol. 1999;13:537-45 pubmed..These findings have important implications for understanding placental function and may be relevant in a range of disease states. ..
- Huang H, Shen J, Vinores S. Blockade of VEGFR1 and 2 suppresses pathological angiogenesis and vascular leakage in the eye. PLoS ONE. 2011;6:e21411 pubmed publisherb>VEGFR1 and 2 signaling have both been increasingly shown to mediate complications of ischemic retinopathies, including retinopathy of prematurity (ROP), age-related macular degeneration (AMD), and diabetic retinopathy (DR)...
- Kaplan R, Riba R, Zacharoulis S, Bramley A, Vincent L, Costa C, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. 2005;438:820-7 pubmed..Here we demonstrate that bone marrow-derived haematopoietic progenitor cells that express vascular endothelial growth factor receptor 1 (VEGFR1; also known as Flt1) home to tumour-specific pre-metastatic sites and form cellular ..
- Carmeliet P, Ng Y, Nuyens D, Theilmeier G, Brusselmans K, Cornelissen I, et al. Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188. Nat Med. 1999;5:495-502 pubmed
- Kendall R, Thomas K. Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc Natl Acad Sci U S A. 1993;90:10705-9 pubmed
- Yoon D, Pastore Y, Divoky V, Liu E, Mlodnicka A, Rainey K, et al. Hypoxia-inducible factor-1 deficiency results in dysregulated erythropoiesis signaling and iron homeostasis in mouse development. J Biol Chem. 2006;281:25703-11 pubmed..These results identify a novel role for HIF-1 in the regulation of iron homeostasis and reveal unexpected regulatory differences in Epo/EpoR signaling in yolk sac and embryonic erythropoiesis. ..
- Zhang H, Palmer R, Gao X, Kreidberg J, Gerald W, Hsiao L, et al. Transcriptional activation of placental growth factor by the forkhead/winged helix transcription factor FoxD1. Curr Biol. 2003;13:1625-9 pubmed..The contribution of PlGF toward stromal signals that regulate epithelial differentiation suggests novel functions for a growth factor previously implicated in reactive angiogenesis. ..
- Imoukhuede P, Dokun A, Annex B, Popel A. Endothelial cell-by-cell profiling reveals the temporal dynamics of VEGFR1 and VEGFR2 membrane localization after murine hindlimb ischemia. Am J Physiol Heart Circ Physiol. 2013;304:H1085-93 pubmed publisher..Flow cytometry was used to measure and compare the ex vivo surface localization of VEGFR1 and VEGFR2 on CD31(+)/CD34(+) ECs 3 and 10 days after unilateral ligation of the femoral artery...
- Banerjee I, Zhang J, Moore Morris T, Lange S, Shen T, Dalton N, et al. Thymosin beta 4 is dispensable for murine cardiac development and function. Circ Res. 2012;110:456-64 pubmed publisher..5-Cre and ?MHC-Cre, were also found to have no phenotype. We conclude that T?4 is dispensable for embryonic viability, heart development, coronary vessel development, and adult myocardial function. ..
- Choi K, Wall C, Hanratty R, Keller G. Isolation of a gene encoding a novel receptor tyrosine kinase from differentiated embryonic stem cells. Oncogene. 1994;9:1261-6 pubmed..On the basis of sequence homology, EmRK2 is likely to be the mouse homologue of human flt, a receptor for vascular endothelial growth factor, and as such, could encode an endothelial cell specific receptor tyrosine kinase. ..
- Matsui Y, Amano H, Ito Y, Eshima K, Tamaki H, Ogawa F, et al. The role of vascular endothelial growth factor receptor-1 signaling in compensatory contralateral lung growth following unilateral pneumonectomy. Lab Invest. 2015;95:456-68 pubmed publisher..The mobilization of progenitor cells expressing VEGFR1(+) cells from bone marrow and the recruitment of these cells to lung tissue were also suppressed in the TK(-/-) ..