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Gene Review

Kdr  -  kinase insert domain receptor

Rattus norvegicus

Synonyms: FLK-1, Fetal liver kinase 1, Flk1, Protein-tyrosine kinase receptor flk-1, VEGFR-2, ...
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Disease relevance of Kdr


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

  • Nitric oxide, VEGF, and VEGFR-2: interactions in activity-induced angiogenesis in rat skeletal muscle [17].
  • Flt-1, Flk-1, and ACE-containing cells were detected in 3% O2-treated explants, whereas 20% O2 explants were virtually negative [18].
  • To determine whether this process is angiogenesis-dependent, we assessed the effects of SU5416, a specific inhibitor of VEGF receptor-2, in portal hypertensive rats [19].
  • Expression of vascular endothelial growth factor and its receptors Flt-1 and KDR/Flk-1 in chronic cyclosporine nephrotoxicity [20].
  • These anti-VEGF effects were partly reproduced by pharmacological inhibitors such as PD98059 and PTK787, suggesting that PCK3145 inhibits the tyrosine kinase activity associated to VEGFR-2, which in turn prevents intracellular signalling through the MAPK cascade [21].

Regulatory relationships of Kdr

  • RESULTS: VEGFR-2 mRNA and protein expression were up-regulated without an increase in VEGF or VEGFR-1 expression [1].
  • Characterization of indolinones which preferentially inhibit VEGF-C- and VEGF-D-induced activation of VEGFR-3 rather than VEGFR-2 [22].
  • Inhibition of VEGFR-2 blocked the activation of Akt/PKB [23].

Other interactions of Kdr

  • It was also noted that Flt-1/Flk-1 and VEGF-positive vessels often were negative for SMI-71, a marker for vessels in areas with blood-brain barrier (BBB) [24].
  • Mechanical stretch induces upregulation of the key tyrosine kinase receptors Flk-1, Tie-2, and Tie-1 in vascular EC, which underlies the increase in sensitivity of EC to growth factors and, therefore, facilitates angiogenesis [25].
  • In the lumbar segment, we observed that reduced Flk-1 expression and hypoxic challenge for 7 days resulted in approximately 50% loss of motor neurons, in which the activation of Akt and ERK, that is, increased levels of phosphorylated-Akt and of phosphorylated-ERK by hypoxia, was markedly inhibited [16].
  • Strikingly, some of the cells infiltrating the treated muscles were found positive for markers of activated endothelial precursors (VEGFR-2/KDR and Tie-2) and for c-kit, an antigen expressed by pluripotent bone marrow stem cells [26].
  • In the transplanted islets, staining for VEGF, HGF, and c-Met was positive, but Flk-1 was not stained [27].

Analytical, diagnostic and therapeutic context of Kdr


  1. Renal ischemia-reperfusion increases endothelial VEGFR-2 without increasing VEGF or VEGFR-1 expression. Kanellis, J., Paizis, K., Cox, A.J., Stacker, S.A., Gilbert, R.E., Cooper, M.E., Power, D.A. Kidney Int. (2002) [Pubmed]
  2. Vascular endothelial growth factor and its receptors in control and diabetic rat eyes. Gilbert, R.E., Vranes, D., Berka, J.L., Kelly, D.J., Cox, A., Wu, L.L., Stacker, S.A., Cooper, M.E. Lab. Invest. (1998) [Pubmed]
  3. Vascular endothelial growth factor mediates vasogenic edema in acute lead encephalopathy. Hossain, M.A., Russell, J.C., Miknyoczki, S., Ruggeri, B., Lal, B., Laterra, J. Ann. Neurol. (2004) [Pubmed]
  4. Cell type specific upregulation of vascular endothelial growth factor in an MCA-occlusion model of cerebral infarct. Plate, K.H., Beck, H., Danner, S., Allegrini, P.R., Wiessner, C. J. Neuropathol. Exp. Neurol. (1999) [Pubmed]
  5. Adenovirus encoding vascular endothelial growth factor-D induces tissue-specific vascular patterns in vivo. Byzova, T.V., Goldman, C.K., Jankau, J., Chen, J., Cabrera, G., Achen, M.G., Stacker, S.A., Carnevale, K.A., Siemionow, M., Deitcher, S.R., DiCorleto, P.E. Blood (2002) [Pubmed]
  6. Vascular endothelial growth factor induces activation and subcellular translocation of focal adhesion kinase (p125FAK) in cultured rat cardiac myocytes. Takahashi, N., Seko, Y., Noiri, E., Tobe, K., Kadowaki, T., Sabe, H., Yazaki, Y. Circ. Res. (1999) [Pubmed]
  7. Vascular endothelial growth factor increases the mitogenic response to fibroblast growth factor-2 in vascular smooth muscle cells in vivo via expression of fms-like tyrosine kinase-1. Couper, L.L., Bryant, S.R., Eldrup-Jørgensen, J., Bredenberg, C.E., Lindner, V. Circ. Res. (1997) [Pubmed]
  8. Direct stimulation of adult neural stem cells in vitro and neurogenesis in vivo by vascular endothelial growth factor. Schänzer, A., Wachs, F.P., Wilhelm, D., Acker, T., Cooper-Kuhn, C., Beck, H., Winkler, J., Aigner, L., Plate, K.H., Kuhn, H.G. Brain Pathol. (2004) [Pubmed]
  9. Alterations in the immunohistochemical distribution patterns of vascular endothelial growth factor receptors Flk1 and Flt1 in bleomycin-induced rat lung fibrosis. Fehrenbach, H., Haase, M., Kasper, M., Koslowski, R., Schuh, D., Müller, M. Virchows Arch. (1999) [Pubmed]
  10. PTK787/ZK222584, an inhibitor of vascular endothelial growth factor receptor tyrosine kinases, decreases glioma growth and vascularization. Goldbrunner, R.H., Bendszus, M., Wood, J., Kiderlen, M., Sasaki, M., Tonn, J.C. Neurosurgery (2004) [Pubmed]
  11. Resveratrol ameliorates myocardial damage by inducing vascular endothelial growth factor-angiogenesis and tyrosine kinase receptor Flk-1. Fukuda, S., Kaga, S., Zhan, L., Bagchi, D., Das, D.K., Bertelli, A., Maulik, N. Cell Biochem. Biophys. (2006) [Pubmed]
  12. Flk-1 specific kinase inhibitor (SU5416) inhibited the growth of GS-9L glioma in rat brain and prolonged the survival. Takamoto, T., Sasaki, M., Kuno, T., Tamaki, N. The Kobe journal of medical sciences. (2001) [Pubmed]
  13. Nitric oxide modulates vascular endothelial growth factor and receptors in chronic cyclosporine nephrotoxicity. Shihab, F.S., Bennett, W.M., Isaac, J., Yi, H., Andoh, T.F. Kidney Int. (2003) [Pubmed]
  14. Attenuation of the exercise-induced increase in skeletal muscle Flt-1 mRNA by nitric oxide synthase inhibition. Gavin, T.P., Wagner, P.D. Acta Physiol. Scand. (2002) [Pubmed]
  15. Rapid transactivation of the vascular endothelial growth factor receptor KDR/Flk-1 by the bradykinin B2 receptor contributes to endothelial nitric-oxide synthase activation in cardiac capillary endothelial cells. Thuringer, D., Maulon, L., Frelin, C. J. Biol. Chem. (2002) [Pubmed]
  16. Reduction of a vascular endothelial growth factor receptor, fetal liver kinase-1, by antisense oligonucleotides induces motor neuron death in rat spinal cord exposed to hypoxia. Shiote, M., Nagano, I., Ilieva, H., Murakami, T., Narai, H., Ohta, Y., Nagata, T., Shoji, M., Abe, K. Neuroscience (2005) [Pubmed]
  17. Nitric oxide, VEGF, and VEGFR-2: interactions in activity-induced angiogenesis in rat skeletal muscle. Milkiewicz, M., Hudlicka, O., Brown, M.D., Silgram, H. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  18. Oxygen regulates vascular endothelial growth factor-mediated vasculogenesis and tubulogenesis. Tufro-McReddie, A., Norwood, V.F., Aylor, K.W., Botkin, S.J., Carey, R.M., Gomez, R.A. Dev. Biol. (1997) [Pubmed]
  19. Inhibition of VEGF receptor-2 decreases the development of hyperdynamic splanchnic circulation and portal-systemic collateral vessels in portal hypertensive rats. Fernandez, M., Mejias, M., Angermayr, B., Garcia-Pagan, J.C., Rodés, J., Bosch, J. J. Hepatol. (2005) [Pubmed]
  20. Expression of vascular endothelial growth factor and its receptors Flt-1 and KDR/Flk-1 in chronic cyclosporine nephrotoxicity. Shihab, F.S., Bennett, W.M., Yi, H., Andoh, T.F. Transplantation (2001) [Pubmed]
  21. A prostate secretory protein94-derived synthetic peptide PCK3145 inhibits VEGF signalling in endothelial cells: implication in tumor angiogenesis. Lamy, S., Ruiz, M.T., Wisniewski, J., Garde, S., Rabbani, S.A., Panchal, C., Wu, J.J., Annabi, B. Int. J. Cancer (2006) [Pubmed]
  22. Characterization of indolinones which preferentially inhibit VEGF-C- and VEGF-D-induced activation of VEGFR-3 rather than VEGFR-2. Kirkin, V., Mazitschek, R., Krishnan, J., Steffen, A., Waltenberger, J., Pepper, M.S., Giannis, A., Sleeman, J.P. Eur. J. Biochem. (2001) [Pubmed]
  23. Neuroprotection by hypoxic preconditioning requires sequential activation of vascular endothelial growth factor receptor and Akt. Wick, A., Wick, W., Waltenberger, J., Weller, M., Dichgans, J., Schulz, J.B. J. Neurosci. (2002) [Pubmed]
  24. VEGF and VEGF receptor expression after experimental brain contusion in rat. Sköld, M.K., von Gertten, C., Sandberg-Nordqvist, A.C., Mathiesen, T., Holmin, S. J. Neurotrauma (2005) [Pubmed]
  25. Stretch induces upregulation of key tyrosine kinase receptors in microvascular endothelial cells. Zheng, W., Christensen, L.P., Tomanek, R.J. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  26. Induction of functional neovascularization by combined VEGF and angiopoietin-1 gene transfer using AAV vectors. Arsic, N., Zentilin, L., Zacchigna, S., Santoro, D., Stanta, G., Salvi, A., Sinagra, G., Giacca, M. Mol. Ther. (2003) [Pubmed]
  27. Immunohistochemical analysis of vascular endothelial growth factor and hepatocyte growth factor, and their receptors, in transplanted islets in rats. Watanabe, H., Sumi, S., Kitamura, Y., Nio, Y., Higami, T. Surgery today. (2003) [Pubmed]
  28. Aging and orchidectomy modulate expression of VEGF receptors (Flt-1 and Flk-1) on corpus cavernosum of the rat. Neves, D., Santos, J., Tomada, N., Almeida, H., Vendeira, P. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  29. Increased angiogenesis and expression of vascular endothelial growth factor during scarless repair. Colwell, A.S., Beanes, S.R., Soo, C., Dang, C., Ting, K., Longaker, M.T., Atkinson, J.B., Lorenz, H.P. Plast. Reconstr. Surg. (2005) [Pubmed]
  30. Vascular endothelial growth factor induces nephrogenesis and vasculogenesis. Tufro, A., Norwood, V.F., Carey, R.M., Gomez, R.A. J. Am. Soc. Nephrol. (1999) [Pubmed]
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