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Gene Review

Flt1  -  FMS-related tyrosine kinase 1

Rattus norvegicus

Synonyms: FLT-1, Flt-1, Fms-like tyrosine kinase 1, Tyrosine-protein kinase receptor FLT, VEGFR-1, ...
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Disease relevance of Flt1


High impact information on Flt1

  • In contrast, overexpression of placental growth factor, which signals through Flt1 but not kinase insert domain protein receptors (KDRs), had negative effects on neurogenesis and inhibited learning, although it similarly increased endothelial cell proliferation [6].
  • In addition, however, the demonstration of functional VEGF receptor expression by Schwann cells indicates a direct effect of VEGF on neural integrity as well [7].
  • Here we report the unexpected finding that treatment with truncated soluble Flt-1 receptors, which inhibit vascular endothelial growth factor (VEGF) bioactivity, resulted in virtually complete suppression of CL angiogenesis in a rat model of hormonally induced ovulation [8].
  • The VEGF receptor inhibitor SU5416 induced alveolar septal cell apoptosis but did not inhibit lung cell proliferation [5].
  • We conclude that VEGF in the isolated perfused lung acts as an early gene in response to hypoxia and that lung VEGF and VEGF receptor mRNA levels are influenced by hypoxia and NO-dependent mechanisms [9].

Chemical compound and disease context of Flt1


Biological context of Flt1


Anatomical context of Flt1

  • In control lungs, Flt1 immunoreactivity was present in ciliated bronchial epithelium and type 2 pneumocytes, Flk1 in Clara cells, and VEGF in Clara cells and type 2 pneumocytes [1].
  • A new communication system between hepatocytes and sinusoidal endothelial cells in liver through vascular endothelial growth factor and Flt tyrosine kinase receptor family (Flt-1 and KDR/Flk-1) [14].
  • 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) [2].
  • Attenuation of the exercise-induced increase in skeletal muscle Flt-1 mRNA by nitric oxide synthase inhibition [11].
  • On the other hand, VEGFR-1 was demonstrated in smooth muscle fibers, particularly in those that surround vessel endothelium, the endothelial expression being very low in control and orchidectomized rats [15].

Associations of Flt1 with chemical compounds


Regulatory relationships of Flt1

  • RESULTS: VEGFR-2 mRNA and protein expression were up-regulated without an increase in VEGF or VEGFR-1 expression [19].
  • VEGF and VEGF receptor expression are upregulated by hypoxia in vivo and the role of VEGF in hypoxia-induced angiogenesis has been extensively studied in a variety of disease entities [20].
  • In this study AngII upregulated VEGF and Flt-1 expression in myoFb, but not KDR; this was mediated predominantly by AT1-receptor [21].

Other interactions of Flt1


Analytical, diagnostic and therapeutic context of Flt1


  1. 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]
  2. 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]
  3. 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]
  4. Expression of vascular endothelial growth factor and its receptors during lung carcinogenesis by N-nitrosobis(2-hydroxypropyl)amine in rats. Takahama, M., Tsutsumi, M., Tsujiuchi, T., Kido, A., Sakitani, H., Iki, K., Taniguchi, S., Kitamura, S., Konishi, Y. Mol. Carcinog. (1999) [Pubmed]
  5. Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. Kasahara, Y., Tuder, R.M., Taraseviciene-Stewart, L., Le Cras, T.D., Abman, S., Hirth, P.K., Waltenberger, J., Voelkel, N.F. J. Clin. Invest. (2000) [Pubmed]
  6. VEGF links hippocampal activity with neurogenesis, learning and memory. Cao, L., Jiao, X., Zuzga, D.S., Liu, Y., Fong, D.M., Young, D., During, M.J. Nat. Genet. (2004) [Pubmed]
  7. Favorable effect of VEGF gene transfer on ischemic peripheral neuropathy. Schratzberger, P., Schratzberger, G., Silver, M., Curry, C., Kearney, M., Magner, M., Alroy, J., Adelman, L.S., Weinberg, D.H., Ropper, A.H., Isner, J.M. Nat. Med. (2000) [Pubmed]
  8. Vascular endothelial growth factor is essential for corpus luteum angiogenesis. Ferrara, N., Chen, H., Davis-Smyth, T., Gerber, H.P., Nguyen, T.N., Peers, D., Chisholm, V., Hillan, K.J., Schwall, R.H. Nat. Med. (1998) [Pubmed]
  9. Increased gene expression for VEGF and the VEGF receptors KDR/Flk and Flt in lungs exposed to acute or to chronic hypoxia. Modulation of gene expression by nitric oxide. Tuder, R.M., Flook, B.E., Voelkel, N.F. J. Clin. Invest. (1995) [Pubmed]
  10. The involvement of VEGF receptors and MAPK in the cannabinoid potentiation of Ca2+ flux into N18TG2 neuroblastoma cells. Rubovitch, V., Gafni, M., Sarne, Y. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  11. 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]
  12. Differential in vivo and in vitro expression of vascular endothelial growth factor (VEGF)-C and VEGF-D in tumors and its relationship to lymphatic metastasis in immunocompetent rats. Krishnan, J., Kirkin, V., Steffen, A., Hegen, M., Weih, D., Tomarev, S., Wilting, J., Sleeman, J.P. Cancer Res. (2003) [Pubmed]
  13. 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]
  14. A new communication system between hepatocytes and sinusoidal endothelial cells in liver through vascular endothelial growth factor and Flt tyrosine kinase receptor family (Flt-1 and KDR/Flk-1). Yamane, A., Seetharam, L., Yamaguchi, S., Gotoh, N., Takahashi, T., Neufeld, G., Shibuya, M. Oncogene (1994) [Pubmed]
  15. 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]
  16. Vasopressin V1a receptor signaling in a rat choroid plexus cell line. Battle, T., Preisser, L., Marteau, V., Meduri, G., Lambert, M., Nitschke, R., Brown, P.D., Corman, B. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  17. 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]
  18. 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]
  19. 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]
  20. Increased vascular endothelial growth factor production in the lungs of rats with hypoxia-induced pulmonary hypertension. Christou, H., Yoshida, A., Arthur, V., Morita, T., Kourembanas, S. Am. J. Respir. Cell Mol. Biol. (1998) [Pubmed]
  21. Cardiac myofibroblasts: a novel source of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and KDR. Chintalgattu, V., Nair, D.M., Katwa, L.C. J. Mol. Cell. Cardiol. (2003) [Pubmed]
  22. Endogenous VEGF-A is responsible for mitogenic effects of MCP-1 on vascular smooth muscle cells. Parenti, A., Bellik, L., Brogelli, L., Filippi, S., Ledda, F. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  23. Differential regulation of vascular endothelial growth factor and its receptor fms-like-tyrosine kinase is mediated by nitric oxide in rat renal mesangial cells. Frank, S., Stallmeyer, B., Kämpfer, H., Schaffner, C., Pfeilschifter, J. Biochem. J. (1999) [Pubmed]
  24. 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]
  25. Effect of hypoxia and endothelial loss on vascular smooth muscle cell responsiveness to VEGF-A: role of flt-1/VEGF-receptor-1. Parenti, A., Brogelli, L., Filippi, S., Donnini, S., Ledda, F. Cardiovasc. Res. (2002) [Pubmed]
  26. Aldosterone impairs bone marrow-derived progenitor cell formation. Marumo, T., Uchimura, H., Hayashi, M., Hishikawa, K., Fujita, T. Hypertension (2006) [Pubmed]
  27. 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]
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