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Gene Review

Kdr  -  kinase insert domain protein receptor

Mus musculus

Synonyms: 6130401C07, FLK-1, Fetal liver kinase 1, Flk-1, Flk1, ...
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Disease relevance of Kdr

  • Systemic administration of antibodies against the transmembrane receptor Flk-1 but not Flt-1 protected against sepsis mortality [1].
  • When similar combination was applied to the H460 lung cancer xenograft model in nude mice, loss of radiation-induced phosphorylated Flk-1 was observed in the combination treatment group, which also showed a large decrease in tumor vascular density by staining of the von Willebrand factor [2].
  • Overexpression of VEGF 121 in immortalized endothelial cells causes conversion to slowly growing angiosarcoma and high level expression of the VEGF receptors VEGFR-1 and VEGFR-2 in vivo [3].
  • Circulating leukocytes and thrombocytes were increased in irradiated SCID (H2K(d)) mice transplanted with ES cell-derived Flk1+ cells compared with vehicle-injected control mice [4].
  • Increased expression of KDR/Flk-1 (VEGFR-2) in murine model of ischemia-induced retinal neovascularization [5].
  • We also examined whether ischaemic preconditioning (PC), a novel method to induce cardioprotection against ischaemia reperfusion injury, through stimulating the VEGF signalling pathway might function in Flk-1(+/-) mice [6].

High impact information on Kdr


Chemical compound and disease context of Kdr


Biological context of Kdr


Anatomical context of Kdr


Associations of Kdr with chemical compounds


Physical interactions of Kdr


Regulatory relationships of Kdr


Other interactions of Kdr


Analytical, diagnostic and therapeutic context of Kdr

  • This response may be the consequence of an increased number of VEGFR-2 positive cells at an early stage of EB development, a finding corroborated by both immunostaining and real-time RT-PCR [27].
  • Microarray analysis of VEGFR-2/CD31 positive cells after 6 days of differentiation revealed numerous changes of expression of genes relating to an endothelial/hematopoietic phenotype in response to Shb overexpression [27].
  • Administration of either anti-VEGFR-1 or anti-VEGFR-2 alone failed to inhibit allograft rejection [31].
  • CONCLUSION: The Flk1+ hematopoietic cells derived from ES cells reconstitute hematopoiesis in vivo and may become an alternative donor source for bone marrow transplantation [4].
  • Northern blot analysis demonstrated that the mRNA levels of KDR/Flk-1 were greater in the neovascular retina of hypoxic animals than in control animals [5].


  1. Vascular endothelial growth factor is an important determinant of sepsis morbidity and mortality. Yano, K., Liaw, P.C., Mullington, J.M., Shih, S.C., Okada, H., Bodyak, N., Kang, P.M., Toltl, L., Belikoff, B., Buras, J., Simms, B.T., Mizgerd, J.P., Carmeliet, P., Karumanchi, S.A., Aird, W.C. J. Exp. Med. (2006) [Pubmed]
  2. Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitor AZD2171 and Fractionated Radiotherapy in Mouse Models of Lung Cancer. Cao, C., Albert, J.M., Geng, L., Ivy, P.S., Sandler, A., Johnson, D.H., Lu, B. Cancer Res. (2006) [Pubmed]
  3. Overexpression of VEGF 121 in immortalized endothelial cells causes conversion to slowly growing angiosarcoma and high level expression of the VEGF receptors VEGFR-1 and VEGFR-2 in vivo. Arbiser, J.L., Larsson, H., Claesson-Welsh, L., Bai, X., LaMontagne, K., Weiss, S.W., Soker, S., Flynn, E., Brown, L.F. Am. J. Pathol. (2000) [Pubmed]
  4. Flk1+ cells derived from mouse embryonic stem cells reconstitute hematopoiesis in vivo in SCID mice. Miyagi, T., Takeno, M., Nagafuchi, H., Takahashi, M., Suzuki, N. Exp. Hematol. (2002) [Pubmed]
  5. Increased expression of KDR/Flk-1 (VEGFR-2) in murine model of ischemia-induced retinal neovascularization. Suzuma, K., Takagi, H., Otani, A., Suzuma, I., Honda, Y. Microvasc. Res. (1998) [Pubmed]
  6. Heterozygous disruption of Flk-1 receptor leads to myocardial ischaemia reperfusion injury in mice: application of affymetrix gene chip analysis. Thirunavukkarasu, M., Addya, S., Juhasz, B., Pant, R., Zhan, L., Surrey, S., Maulik, G., Menon, V.P., Maulik, N. J. Cell. Mol. Med. (2008) [Pubmed]
  7. A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis. Shalaby, F., Ho, J., Stanford, W.L., Fischer, K.D., Schuh, A.C., Schwartz, L., Bernstein, A., Rossant, J. Cell (1997) [Pubmed]
  8. VEGF modulates erythropoiesis through regulation of adult hepatic erythropoietin synthesis. Tam, B.Y., Wei, K., Rudge, J.S., Hoffman, J., Holash, J., Park, S.K., Yuan, J., Hefner, C., Chartier, C., Lee, J.S., Jiang, S., Niyak, N.R., Kuypers, F.A., Ma, L., Sundram, U., Wu, G., Garcia, J.A., Schrier, S.L., Maher, J.J., Johnson, R.S., Yancopoulos, G.D., Mulligan, R.C., Kuo, C.J. Nat. Med. (2006) [Pubmed]
  9. ZD6474, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, inhibits growth of experimental lung metastasis and production of malignant pleural effusions in a non-small cell lung cancer model. Matsumori, Y., Yano, S., Goto, H., Nakataki, E., Wedge, S.R., Ryan, A.J., Sone, S. Oncol. Res. (2006) [Pubmed]
  10. Active immunization against the vascular endothelial growth factor receptor flk1 inhibits tumor angiogenesis and metastasis. Li, Y., Wang, M.N., Li, H., King, K.D., Bassi, R., Sun, H., Santiago, A., Hooper, A.T., Bohlen, P., Hicklin, D.J. J. Exp. Med. (2002) [Pubmed]
  11. Inhibition of ovarian tumor growth by gene therapy with recombinant soluble vascular endothelial growth factor receptor 2. Wu, Y., Li, Z.Y., Zhao, X., Kan, B., Wei, Y.Q. Hum. Gene Ther. (2006) [Pubmed]
  12. Dominant-negative inhibition of Flk-1 suppresses the growth of many tumor types in vivo. Millauer, B., Longhi, M.P., Plate, K.H., Shawver, L.K., Risau, W., Ullrich, A., Strawn, L.M. Cancer Res. (1996) [Pubmed]
  13. Effect of the vascular endothelial growth factor receptor-2 antibody DC101 plus gemcitabine on growth, metastasis and angiogenesis of human pancreatic cancer growing orthotopically in nude mice. Bruns, C.J., Shrader, M., Harbison, M.T., Portera, C., Solorzano, C.C., Jauch, K.W., Hicklin, D.J., Radinsky, R., Ellis, L.M. Int. J. Cancer (2002) [Pubmed]
  14. Combinatorial effects of Flk1 and Tal1 on vascular and hematopoietic development in the mouse. Ema, M., Faloon, P., Zhang, W.J., Hirashima, M., Reid, T., Stanford, W.L., Orkin, S., Choi, K., Rossant, J. Genes Dev. (2003) [Pubmed]
  15. Roles of vascular endothelial growth factor receptor 3 signaling in differentiation of mouse embryonic stem cell-derived vascular progenitor cells into endothelial cells. Suzuki, H., Watabe, T., Kato, M., Miyazawa, K., Miyazono, K. Blood (2005) [Pubmed]
  16. Vascular endothelial growth factor (VEGF)-C differentially affects tumor vascular function and leukocyte recruitment: role of VEGF-receptor 2 and host VEGF-A. Kadambi, A., Mouta Carreira, C., Yun, C.O., Padera, T.P., Dolmans, D.E., Carmeliet, P., Fukumura, D., Jain, R.K. Cancer Res. (2001) [Pubmed]
  17. Absence of erythrogenesis and vasculogenesis in Plcg1-deficient mice. Liao, H.J., Kume, T., McKay, C., Xu, M.J., Ihle, J.N., Carpenter, G. J. Biol. Chem. (2002) [Pubmed]
  18. A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit. Matthews, W., Jordan, C.T., Gavin, M., Jenkins, N.A., Copeland, N.G., Lemischka, I.R. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  19. Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. Quinn, T.P., Peters, K.G., De Vries, C., Ferrara, N., Williams, L.T. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  20. A chemically defined culture of VEGFR2+ cells derived from embryonic stem cells reveals the role of VEGFR1 in tuning the threshold for VEGF in developing endothelial cells. Hirashima, M., Ogawa, M., Nishikawa, S., Matsumura, K., Kawasaki, K., Shibuya, M., Nishikawa, S. Blood (2003) [Pubmed]
  21. Vascular endothelial growth factor and hepatocyte regeneration in acetaminophen toxicity. Donahower, B., McCullough, S.S., Kurten, R., Lamps, L.W., Simpson, P., Hinson, J.A., James, L.P. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  22. Vascular permeability induced by VEGF family members in vivo: Role of endogenous PAF and NO synthesis. Brkovic, A., Sirois, M.G. J. Cell. Biochem. (2007) [Pubmed]
  23. A vascular endothelial growth factor receptor-2 kinase inhibitor potentiates the activity of the conventional chemotherapeutic agents paclitaxel and doxorubicin in tumor xenograft models. Emanuel, S., Gruninger, R.H., Fuentes-Pesquera, A., Connolly, P.J., Seamon, J.A., Hazel, S., Tominovich, R., Hollister, B., Napier, C., D'Andrea, M.R., Reuman, M., Bignan, G., Tuman, R., Johnson, D., Moffatt, D., Batchelor, M., Foley, A., O'Connell, J., Allen, R., Perry, M., Jolliffe, L., Middleton, S.A. Mol. Pharmacol. (2004) [Pubmed]
  24. VE-cadherin increases the half-life of VEGF receptor 2. Calera, M.R., Venkatakrishnan, A., Kazlauskas, A. Exp. Cell Res. (2004) [Pubmed]
  25. Cooperative interaction of hypoxia-inducible factor-2alpha (HIF-2alpha ) and Ets-1 in the transcriptional activation of vascular endothelial growth factor receptor-2 (Flk-1). Elvert, G., Kappel, A., Heidenreich, R., Englmeier, U., Lanz, S., Acker, T., Rauter, M., Plate, K., Sieweke, M., Breier, G., Flamme, I. J. Biol. Chem. (2003) [Pubmed]
  26. Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice. Veikkola, T., Jussila, L., Makinen, T., Karpanen, T., Jeltsch, M., Petrova, T.V., Kubo, H., Thurston, G., McDonald, D.M., Achen, M.G., Stacker, S.A., Alitalo, K. EMBO J. (2001) [Pubmed]
  27. Shb promotes blood vessel formation in embryoid bodies by augmenting vascular endothelial growth factor receptor-2 and platelet-derived growth factor receptor-beta signaling. Rolny, C., Lu, L., Agren, N., Nilsson, I., Roe, C., Webb, G.C., Welsh, M. Exp. Cell Res. (2005) [Pubmed]
  28. Involvement of Runx1 in the down-regulation of fetal liver kinase-1 expression during transition of endothelial cells to hematopoietic cells. Hirai, H., Samokhvalov, I.M., Fujimoto, T., Nishikawa, S., Imanishi, J., Nishikawa, S. Blood (2005) [Pubmed]
  29. Modulation of VEGFR-2-mediated endothelial-cell activity by VEGF-C/VEGFR-3. Matsumura, K., Hirashima, M., Ogawa, M., Kubo, H., Hisatsune, H., Kondo, N., Nishikawa, S., Chiba, T., Nishikawa, S. Blood (2003) [Pubmed]
  30. Deregulation of Flk-1/vascular endothelial growth factor receptor-2 in fibroblast growth factor receptor-1-deficient vascular stem cell development. Magnusson, P., Rolny, C., Jakobsson, L., Wikner, C., Wu, Y., Hicklin, D.J., Claesson-Welsh, L. J. Cell. Sci. (2004) [Pubmed]
  31. Function of the vascular endothelial growth factor receptors Flt-1 and Flk-1/KDR in the alloimmune response in vivo. Sho, M., Akashi, S., Kanehiro, H., Hamada, K., Kashizuka, H., Ikeda, N., Nomi, T., Kuzumoto, Y., Tsurui, Y., Yoshiji, H., Wu, Y., Hicklin, D.J., Briscoe, D.M., Nakajima, Y. Transplantation (2005) [Pubmed]
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