Gene Symbol: kdr
Description: kinase insert domain receptor (a type III receptor tyrosine kinase)
Alias: flk1, flk1b, kdrb, si:busm1-205d10.1, si:ch211-254j6.1, si:ch211-278f21.4, vegfr2b, wu:fc31a09, vascular endothelial growth factor receptor 2, FLK-1b, VEGFR-2 homolog B, fetal liver kinase 1b, kinase insert domain receptor (a type III receptor tyrosine kinase), b, kinase insert domain receptor-B, protein-tyrosine kinase receptor flk-1b, vascular endothelial growth factor receptor 2 homolog B
Species: zebrafish
Products:     kdr

Top Publications

  1. Siegel N, Hoegg S, Salzburger W, Braasch I, Meyer A. Comparative genomics of ParaHox clusters of teleost fishes: gene cluster breakup and the retention of gene sets following whole genome duplications. BMC Genomics. 2007;8:312 pubmed
  2. Bahary N, Goishi K, Stuckenholz C, Weber G, Leblanc J, Schafer C, et al. Duplicate VegfA genes and orthologues of the KDR receptor tyrosine kinase family mediate vascular development in the zebrafish. Blood. 2007;110:3627-36 pubmed
    ..We have isolated a duplicated zebrafish VegfA locus, termed VegfAb, and a duplicate RTK locus with homology to KDR/FLK1 (named Kdrb)...
  3. Covassin L, Villefranc J, Kacergis M, Weinstein B, Lawson N. Distinct genetic interactions between multiple Vegf receptors are required for development of different blood vessel types in zebrafish. Proc Natl Acad Sci U S A. 2006;103:6554-9 pubmed
    ..We also identify an additional zebrafish vegfr-2 ortholog, referred to as kdrb, which can partially compensate for loss of kdra but is dispensable for vascular development in wild-type embryos...
  4. Wythe J, Dang L, Devine W, Boudreau E, Artap S, He D, et al. ETS factors regulate Vegf-dependent arterial specification. Dev Cell. 2013;26:45-58 pubmed publisher
  5. van Rooijen E, Voest E, Logister I, Bussmann J, Korving J, van Eeden F, et al. von Hippel-Lindau tumor suppressor mutants faithfully model pathological hypoxia-driven angiogenesis and vascular retinopathies in zebrafish. Dis Model Mech. 2010;3:343-53 pubmed publisher
    ..increased expression of the duplicated VEGFA orthologs vegfaa and vegfab, and of vegfb and its receptors flt1, kdr and kdr-like, indicating increased vascular endothelial growth factor (Vegf) signaling in vhl mutants...
  6. Li S, Lou S, Lei B, Chan T, Kwan Y, Chan S, et al. Transcriptional profiling of angiogenesis activities of calycosin in zebrafish. Mol Biosyst. 2011;7:3112-21 pubmed publisher
    ..The data have elucidated the connection between morphological observations and genomic evidence, indicating the potential roles of several key signaling pathways in angiogenesis. ..
  7. Bridge G, Monteiro R, Henderson S, Emuss V, Lagos D, Georgopoulou D, et al. The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis. Blood. 2012;120:5063-72 pubmed publisher
    ..Together these results demonstrate that the highly conserved molecular targeting of DLL4 by the miR-30 family regulates angiogenesis. ..
  8. Hu G, Mahady G, Li S, Hoi M, Wang Y, Lee S. Polysaccharides from astragali radix restore chemical-induced blood vessel loss in zebrafish. Vasc Cell. 2012;4:2 pubmed publisher
    ..The rescue effect of ARPs in the zebrafish models was validated by measuring the relative mRNA expressions of Kdrl, Kdr and Flt-1 using real-time PCR...
  9. Tang J, Li S, Li Z, Zhang Z, Hu G, Cheang L, et al. Calycosin promotes angiogenesis involving estrogen receptor and mitogen-activated protein kinase (MAPK) signaling pathway in zebrafish and HUVEC. PLoS ONE. 2010;5:e11822 pubmed publisher
    ..Together, this study revealed, for the first time, that calycosin acts as a selective estrogen receptor modulator (SERM) to promote angiogenesis, at least in part through VEGF-VEGFR2 and MAPK signaling pathways. ..

More Information


  1. Duan J, Hu H, Feng L, Yang X, Sun Z. Silica nanoparticles inhibit macrophage activity and angiogenesis via VEGFR2-mediated MAPK signaling pathway in zebrafish embryos. Chemosphere. 2017;183:483-490 pubmed publisher
    ..related gene, macrophage migration inhibitory factor (MIF) and the angiogenesis related gene, vascular endothelial growth factor receptor 2 (VEGFR2)...
  2. Bower N, Vogrin A, Le Guen L, Chen H, Stacker S, Achen M, et al. Vegfd modulates both angiogenesis and lymphangiogenesis during zebrafish embryonic development. Development. 2017;144:507-518 pubmed publisher
    ..and biochemical binding assays suggest that, during primary angiogenesis, Vegfd influences these phenotypes through Kdr (Vegfr2) rather than Flt4 (Vegfr3)...
  3. Montero Balaguer M, Swirsding K, Orsenigo F, Cotelli F, Mione M, Dejana E. Stable vascular connections and remodeling require full expression of VE-cadherin in zebrafish embryos. PLoS ONE. 2009;4:e5772 pubmed publisher
    ..This suggests that partial internalization or change of function of this protein may strongly affect vascular stability and organization. ..
  4. Lee H, Lin Y, Lai Y, Huang W, Hu J, Tsai J, et al. Glycogen synthase kinase 3 beta in somites plays a role during the angiogenesis of zebrafish embryos. FEBS J. 2014;281:4367-83 pubmed publisher
    ..Thus, both active and inactive forms of Gsk3b mediate the cooperative signaling between Wnt/?-catenin and PI3K/AKT to control VegfAa expression in somites during angiogenesis in zebrafish embryos. ..
  5. Li S, Dang Y, Oi Lam Che G, Kwan Y, Chan S, Leung G, et al. VEGFR tyrosine kinase inhibitor II (VRI) induced vascular insufficiency in zebrafish as a model for studying vascular toxicity and vascular preservation. Toxicol Appl Pharmacol. 2014;280:408-20 pubmed publisher
    ..zebrafish by inhibiting angiogenesis and increasing endothelial cell apoptosis, accompanied by down-regulation of kdr, kdrl and flt-1 genes expression...
  6. Patra C, Kontarakis Z, Kaur H, Rayrikar A, Mukherjee D, Stainier D. The zebrafish ventricle: A hub of cardiac endothelial cells for in vitro cell behavior studies. Sci Rep. 2017;7:2687 pubmed publisher
    ..Such primary cultures will be a useful tool for supplementary in vitro studies on the accumulating zebrafish mutant lines as well as the screening of small molecule libraries on cardiac specific endothelial cells. ..
  7. Cermenati S, Moleri S, Cimbro S, Corti P, Del Giacco L, Amodeo R, et al. Sox18 and Sox7 play redundant roles in vascular development. Blood. 2008;111:2657-66 pubmed
    ..Our data suggest that a defect in arteriovenous identity could be responsible for the formation of telangiectases in patients with HLT. ..
  8. Lai P, Chan J, Kwok H, Cheng L, Yu H, Lau C, et al. Induction of Angiogenesis in Zebrafish Embryos and Proliferation of Endothelial Cells by an Active Fraction Isolated from the Root of Astragalus membranaceus using Bioassay-guided Fractionation. J Tradit Complement Med. 2014;4:239-45 pubmed publisher
    ..effect was evaluated in treated zebrafish embryos by measuring the gene expression of angiogenic markers (VEGFA, KDR, and Flt-1) using real-time polymerase chain reaction (RT-PCR), and in human microvascular endothelial cell (HMEC-1)..
  9. Jensen L, Nakamura M, Bräutigam L, Li X, Liu Y, Samani N, et al. VEGF-B-Neuropilin-1 signaling is spatiotemporally indispensable for vascular and neuronal development in zebrafish. Proc Natl Acad Sci U S A. 2015;112:E5944-53 pubmed publisher
    ..These findings show that VEGF-B is spatiotemporally required for vascular development in zebrafish embryos and that NRP1, but not VEGFR1, mediates the essential signaling. ..
  10. Renz M, Otten C, Faurobert E, Rudolph F, Zhu Y, Boulday G, et al. Regulation of β1 integrin-Klf2-mediated angiogenesis by CCM proteins. Dev Cell. 2015;32:181-90 pubmed publisher
    ..Our work reveals a β1 integrin-Klf2-Egfl7-signaling pathway that is tightly regulated by CCM proteins. This regulation prevents angiogenic overgrowth and ensures the quiescence of endothelial cells. ..
  11. Koenig A, Baltrunaite K, Bower N, Rossi A, Stainier D, Hogan B, et al. Vegfa signaling promotes zebrafish intestinal vasculature development through endothelial cell migration from the posterior cardinal vein. Dev Biol. 2016;411:115-27 pubmed publisher
    ..It is likely that a similar mechanism is utilized during vascularization of other organs. ..
  12. Wild R, Klems A, Takamiya M, Hayashi Y, Strahle U, Ando K, et al. Neuronal sFlt1 and Vegfaa determine venous sprouting and spinal cord vascularization. Nat Commun. 2017;8:13991 pubmed publisher
    ..Conceptually, our data suggest that spinal cord vascularization proceeds from veins involving two-tiered regulation of neuronal sFlt1 and Vegfaa via a novel sprouting mode. ..
  13. Tonon F, Zennaro C, Dapas B, Carraro M, Mariotti M, Grassi G. Rapid and cost-effective xenograft hepatocellular carcinoma model in Zebrafish for drug testing. Int J Pharm. 2016;515:583-591 pubmed publisher
    ..In conclusion, the possibility to test anti HCC/neo-angiogenesis drugs makes our JHH6 model useful to select therapeutic molecules for a highly vascularized tumor such as HCC. ..
  14. Bonventre J, Kung T, White L, Cooper K. Manipulation of the HIF-Vegf pathway rescues methyl tert-butyl ether (MTBE)-induced vascular lesions. Toxicol Appl Pharmacol. 2013;273:623-34 pubmed publisher
    ..The selective toxicity of MTBE toward developing vasculature makes it a potentially useful chemical in the designing of new drugs or in elucidating roles for specific angiogenic proteins in future studies of vascular development. ..
  15. Koltowska K, Lagendijk A, Pichol Thievend C, Fischer J, Francois M, Ober E, et al. Vegfc Regulates Bipotential Precursor Division and Prox1 Expression to Promote Lymphatic Identity in Zebrafish. Cell Rep. 2015;13:1828-41 pubmed publisher
    ..Vegfc drives cell division and Prox1 expression in lymphatic daughter cells, coupling signaling dynamics with daughter cell fate restriction and precursor division. ..
  16. Fukuda M, Ohtani K, Jang S, Yoshizaki T, Mori K, Motomura W, et al. Molecular cloning and functional analysis of scavenger receptor zebrafish CL-P1. Biochim Biophys Acta. 2011;1810:1150-9 pubmed publisher
    ..These results suggest that zCL-P1 might be essential for vasculogenesis during the early embryonic phase in bone fish. ..
  17. Becker P, Sacilotto N, Nornes S, Neal A, Thomas M, Liu K, et al. An Intronic Flk1 Enhancer Directs Arterial-Specific Expression via RBPJ-Mediated Venous Repression. Arterioscler Thromb Vasc Biol. 2016;36:1209-19 pubmed publisher
    The vascular endothelial growth factor (VEGF) receptor Flk1 is essential for vascular development, but the signaling and transcriptional pathways by which its expression is regulated in endothelial cells remain unclear...
  18. Fan Z, Wang D, Yang J, Lin Z, Lin Y, Yang A, et al. Dalbergia odorifera extract promotes angiogenesis through upregulation of VEGFRs and PI3K/MAPK signaling pathways. J Ethnopharmacol. 2017;204:132-141 pubmed publisher
    ..could also restore the injury in zebrafish ISVs area and upregulate the reduced mRNA expression of VEGFRs including kdr, kdrl and flt-1 induced by VEGF receptor kinase inhibitor II (VRI)...
  19. Zhong H, Zou H, Semenov M, Moshinsky D, He X, Huang H, et al. Characterization and development of novel small-molecules inhibiting GSK3 and activating Wnt signaling. Mol Biosyst. 2009;5:1356-60 pubmed publisher
    ..Together, 3F8 and its derivatives could be useful as new reagents and potential therapeutic candidates for GSK3 related diseases. ..
  20. Zhang Z, Li J, Li S, Liu A, Hoi P, Tian H, et al. In vivo angiogenesis screening and mechanism of action of novel tanshinone derivatives produced by one-pot combinatorial modification of natural tanshinone mixture from Salvia miltiorrhiza. PLoS ONE. 2014;9:e100416 pubmed publisher
    ..Our results highlighted the great potential of adopting a newly modified one-pot approach to enhance the chemical diversity and biological activities of constituents from natural products regardless of their abundances. ..
  21. Fang L, Choi S, Baek J, Liu C, Almazan F, Ulrich F, et al. Control of angiogenesis by AIBP-mediated cholesterol efflux. Nature. 2013;498:118-22 pubmed publisher
    ..AIBP- and HDL-mediated cholesterol depletion reduces lipid rafts, interferes with VEGFR2 (also known as KDR) dimerization and signalling and inhibits vascular endothelial growth factor-induced angiogenesis in vitro and ..
  22. Wong W, Matrone G, Tian X, Tomoiaga S, Au K, Meng S, et al. Discovery of novel determinants of endothelial lineage using chimeric heterokaryons. elife. 2017;6: pubmed publisher
    ..These studies provide a systematic and mechanistic approach for identifying key regulators in directed differentiation of pluripotent stem cells to somatic cell lineages. ..
  23. Tu X, Deng Y, Chen J, Hu Q, He C, Jordan J, et al. Screening study on the anti-angiogenic effects of Traditional Chinese Medicine - Part I: Heat-clearing and detoxicating TCM. J Ethnopharmacol. 2016;194:280-287 pubmed publisher
    ..The results provide new insights into their clinical application and therapeutic potential for the management of angiogenesis-dependent diseases such as cancer. ..
  24. Li S, Zhou X, Dang Y, Kwan Y, Chan S, Leung G, et al. Basal Flt1 tyrosine kinase activity is a positive regulator of endothelial survival and vascularization during zebrafish embryogenesis. Biochim Biophys Acta. 2015;1850:373-84 pubmed publisher
    The role of Kdr (VEGFR-2/Flk-1) in vascular formation has been well described, but the role of Flt1 (VEGFR-1) is not well studied and is generally considered as a decoy receptor for trapping VEGF...
  25. Watson O, Novodvorsky P, Gray C, Rothman A, Lawrie A, Crossman D, et al. Blood flow suppresses vascular Notch signalling via dll4 and is required for angiogenesis in response to hypoxic signalling. Cardiovasc Res. 2013;100:252-61 pubmed publisher
    ..These data indicate important differences in hypoxia-driven vs. developmental angiogenesis. ..
  26. Bussmann J, Lawson N, Zon L, Schulte Merker S. Zebrafish VEGF receptors: a guideline to nomenclature. PLoS Genet. 2008;4:e1000064 pubmed publisher
  27. Li S, Dang Y, Zhou X, Huang B, Huang X, Zhang Z, et al. Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway. Sci Rep. 2015;5:16815 pubmed publisher
  28. Fukui H, Hanaoka R, Kawahara A. Noncanonical activity of seryl-tRNA synthetase is involved in vascular development. Circ Res. 2009;104:1253-9 pubmed publisher
    ..Furthermore, the abnormal branching of ISVs in the mutant was suppressed by knockdown of vegfa or vegfr2 (kdra and kdrb). Knockdown of vegfc or vegfr3 rescued the abnormal ISV branching in ko095 mutant...
  29. Zhou Z, Huan L, Zhao W, Tang N, Jin Y, Tang J. Spatholobi Caulis extracts promote angiogenesis in HUVECs in vitro and in zebrafish embryos in vivo via up-regulation of VEGFRs. J Ethnopharmacol. 2017;200:74-83 pubmed publisher
    ..Real-time PCR assay proved that PSC significantly restored the down regulation of VEGFRs including Flt-1, Kdr and Kdrl induced by VRI in zebrafish (P<0.001)...
  30. So J, Hong S, Kim H, Jung S, Lee M, Choi J, et al. Gicerin/Cd146 is involved in zebrafish cardiovascular development and tumor angiogenesis. Genes Cells. 2010;15:1099-110 pubmed publisher
    ..Thus, knock-down of gicerin might have an important implication in controlling tumor angiogenesis. ..
  31. Meng Z, Liu W, Xia Y, Yin H, Zhang C, Su D, et al. The pro-inflammatory signalling regulator Stat4 promotes vasculogenesis of great vessels derived from endothelial precursors. Nat Commun. 2017;8:14640 pubmed publisher
    ..Altogether, our study establishes a role for Stat4 in zebrafish great vessel development, and suggests that Stat4 may serve as a therapeutic target for GV defects. ..
  32. Gao J, Mahapatra C, Mapes C, Khlebnikova M, Wei A, Sepúlveda M. Vascular toxicity of silver nanoparticles to developing zebrafish (Danio rerio). Nanotoxicology. 2016;10:1363-72 pubmed publisher
    ..We propose that PVP-AgNPs temporarily delay embryonic vascular development by interfering with oxygen diffusion into the egg, leading to hypoxic conditions and ER stress. ..
  33. Duan J, Hu H, Zhang Y, Feng L, Shi Y, Miller M, et al. Multi-organ toxicity induced by fine particulate matter PM2.5 in zebrafish (Danio rerio) model. Chemosphere. 2017;180:24-32 pubmed publisher
    ..Genes involved in cardiac function (spaw, supt6h, cmlc1), angiogenesis (vegfr2a, vegfr2b), and neural function (gabrd, chrna3, npy8br) were markedly down-regulated; while genes linked to hepatic ..