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Gene Review

Flt1  -  FMS-like tyrosine kinase 1

Mus musculus

Synonyms: AI323757, Embryonic receptor kinase 2, Emrk2, FLT-1, Flt, ...
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Disease relevance of Flt1


High impact information on Flt1


Chemical compound and disease context of Flt1


Biological context of Flt1


Anatomical context of Flt1

  • These results strongly suggest that the interaction of signals by means of VEGFR-1 and the CSF-1 receptor plays a predominant role not only in osteoclastogenesis but also in the maintenance of bone marrow functions [19].
  • VEGF receptor 1 (VEGFR-1/Flt-1) is a high-affinity tyrosine kinase (TK) receptor for VEGF and regulates angiogenesis as well as monocyte/macrophage functions [19].
  • An alternate VEGFR, VEGFR-1 or neuropilin-1, may modulate adhesion of leukocytes to tumor vessels [20].
  • Because a second high-affinity VEGF receptor, flk-1, produces a positive endothelial proliferation signal, it was logical to ask whether flt-1 affects developmental blood vessel formation by modulating signaling through flk-1 [16].
  • Conversely, stable cell lines expressing activated c-Akt demonstrated ligand-independent capillaries, which were resistant to the treatment with anti-VEGFR-1 blocking antibody [21].

Associations of Flt1 with chemical compounds


Physical interactions of Flt1

  • VEGFR1 may be primarily responsible for binding of VEGF to yolk sac and embryonic tissues, as masking VEGFR2 did not reduce VEGF binding in those areas, and it is interesting that major structural defects were also not found in those regions [27].
  • In contrast, VEGF-A binds VEGFR1 and VEGFR2 and is an essential hemangiogenic factor [28].
  • Both swaps conferred upon Flt-4 the ability to bind VEGF with an affinity nearly identical to that of wild-type Flt-1 [29].

Regulatory relationships of Flt1


Other interactions of Flt1


Analytical, diagnostic and therapeutic context of Flt1


  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. Suppression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor 3 signaling. He, Y., Kozaki, K., Karpanen, T., Koshikawa, K., Yla-Herttuala, S., Takahashi, T., Alitalo, K. J. Natl. Cancer Inst. (2002) [Pubmed]
  3. Trophoblast expression of fms-like tyrosine kinase 1 is not required for the establishment of the maternal-fetal interface in the mouse placenta. Hirashima, M., Lu, Y., Byers, L., Rossant, J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  4. Two independent mechanisms essential for tumor angiogenesis: inhibition of human melanoma xenograft growth by interfering with either the vascular endothelial growth factor receptor pathway or the Tie-2 pathway. Siemeister, G., Schirner, M., Weindel, K., Reusch, P., Menrad, A., Marmé, D., Martiny-Baron, G. Cancer Res. (1999) [Pubmed]
  5. Cartilage repair in a rat model of osteoarthritis through intraarticular transplantation of muscle-derived stem cells expressing bone morphogenetic protein 4 and soluble Flt-1. Matsumoto, T., Cooper, G.M., Gharaibeh, B., Meszaros, L.B., Li, G., Usas, A., Fu, F.H., Huard, J. Arthritis Rheum. (2009) [Pubmed]
  6. Soluble endoglin contributes to the pathogenesis of preeclampsia. Venkatesha, S., Toporsian, M., Lam, C., Hanai, J., Mammoto, T., Kim, Y.M., Bdolah, Y., Lim, K.H., Yuan, H.T., Libermann, T.A., Stillman, I.E., Roberts, D., D'Amore, P.A., Epstein, F.H., Sellke, F.W., Romero, R., Sukhatme, V.P., Letarte, M., Karumanchi, S.A. Nat. Med. (2006) [Pubmed]
  7. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Carmeliet, P., Moons, L., Luttun, A., Vincenti, V., Compernolle, V., De Mol, M., Wu, Y., Bono, F., Devy, L., Beck, H., Scholz, D., Acker, T., DiPalma, T., Dewerchin, M., Noel, A., Stalmans, I., Barra, A., Blacher, S., Vandendriessche, T., Ponten, A., Eriksson, U., Plate, K.H., Foidart, J.M., Schaper, W., Charnock-Jones, D.S., Hicklin, D.J., Herbert, J.M., Collen, D., Persico, M.G. Nat. Med. (2001) [Pubmed]
  8. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Lyden, D., Hattori, K., Dias, S., Costa, C., Blaikie, P., Butros, L., Chadburn, A., Heissig, B., Marks, W., Witte, L., Wu, Y., Hicklin, D., Zhu, Z., Hackett, N.R., Crystal, R.G., Moore, M.A., Hajjar, K.A., Manova, K., Benezra, R., Rafii, S. Nat. Med. (2001) [Pubmed]
  9. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Ferrara, N., Carver-Moore, K., Chen, H., Dowd, M., Lu, L., O'Shea, K.S., Powell-Braxton, L., Hillan, K.J., Moore, M.W. Nature (1996) [Pubmed]
  10. Dual roles of Sema6D in cardiac morphogenesis through region-specific association of its receptor, Plexin-A1, with off-track and vascular endothelial growth factor receptor type 2. Toyofuku, T., Zhang, H., Kumanogoh, A., Takegahara, N., Suto, F., Kamei, J., Aoki, K., Yabuki, M., Hori, M., Fujisawa, H., Kikutani, H. Genes Dev. (2004) [Pubmed]
  11. 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]
  12. 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]
  13. Role of vascular endothelial growth factor receptor 1 in basal adhesion formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in mice. Molinas, C.R., Binda, M.M., Carmeliet, P., Koninckx, P.R. Fertil. Steril. (2004) [Pubmed]
  14. Glomerular expression of nephrin and synaptopodin, but not podocin, is decreased in kidney sections from women with preeclampsia. Garovic, V.D., Wagner, S.J., Petrovic, L.M., Gray, C.E., Hall, P., Sugimoto, H., Kalluri, R., Grande, J.P. Nephrol. Dial. Transplant. (2007) [Pubmed]
  15. Angiotensin II induces soluble fms-Like tyrosine kinase-1 release via calcineurin signaling pathway in pregnancy. Zhou, C.C., Ahmad, S., Mi, T., Xia, L., Abbasi, S., Hewett, P.W., Sun, C., Ahmed, A., Kellems, R.E., Xia, Y. Circ. Res. (2007) [Pubmed]
  16. The vascular endothelial growth factor (VEGF) receptor Flt-1 (VEGFR-1) modulates Flk-1 (VEGFR-2) signaling during blood vessel formation. Roberts, D.M., Kearney, J.B., Johnson, J.H., Rosenberg, M.P., Kumar, R., Bautch, V.L. Am. J. Pathol. (2004) [Pubmed]
  17. Differential transcriptional regulation of the two vascular endothelial growth factor receptor genes. Flt-1, but not Flk-1/KDR, is up-regulated by hypoxia. Gerber, H.P., Condorelli, F., Park, J., Ferrara, N. J. Biol. Chem. (1997) [Pubmed]
  18. Dual epidermal growth factor receptor and vascular endothelial growth factor receptor inhibition with NVP-AEE788 for the treatment of aggressive follicular thyroid cancer. Younes, M.N., Yazici, Y.D., Kim, S., Jasser, S.A., El-Naggar, A.K., Myers, J.N. Clin. Cancer Res. (2006) [Pubmed]
  19. VEGF receptor 1 signaling is essential for osteoclast development and bone marrow formation in colony-stimulating factor 1-deficient mice. Niida, S., Kondo, T., Hiratsuka, S., Hayashi, S., Amizuka, N., Noda, T., Ikeda, K., Shibuya, M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  20. 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]
  21. Fibroblast growth factor-2-mediated capillary morphogenesis of endothelial cells requires signals via Flt-1/vascular endothelial growth factor receptor-1: possible involvement of c-Akt. Kanda, S., Miyata, Y., Kanetake, H. J. Biol. Chem. (2004) [Pubmed]
  22. CEP-7055: a novel, orally active pan inhibitor of vascular endothelial growth factor receptor tyrosine kinases with potent antiangiogenic activity and antitumor efficacy in preclinical models. Ruggeri, B., Singh, J., Gingrich, D., Angeles, T., Albom, M., Yang, S., Chang, H., Robinson, C., Hunter, K., Dobrzanski, P., Jones-Bolin, S., Pritchard, S., Aimone, L., Klein-Szanto, A., Herbert, J.M., Bono, F., Schaeffer, P., Casellas, P., Bourie, B., Pili, R., Isaacs, J., Ator, M., Hudkins, R., Vaught, J., Mallamo, J., Dionne, C. Cancer Res. (2003) [Pubmed]
  23. Podocyte-derived vascular endothelial growth factor mediates the stimulation of alpha3(IV) collagen production by transforming growth factor-beta1 in mouse podocytes. Chen, S., Kasama, Y., Lee, J.S., Jim, B., Marin, M., Ziyadeh, F.N. Diabetes (2004) [Pubmed]
  24. A new class of potent vascular endothelial growth factor receptor tyrosine kinase inhibitors: structure-activity relationships for a series of 9-alkoxymethyl-12-(3-hydroxypropyl)indeno[2,1-a]pyrrolo[3,4-c]carbazole-5-ones and the identification of CEP-5214 and its dimethylglycine ester prodrug clinical candidate CEP-7055. Gingrich, D.E., Reddy, D.R., Iqbal, M.A., Singh, J., Aimone, L.D., Angeles, T.S., Albom, M., Yang, S., Ator, M.A., Meyer, S.L., Robinson, C., Ruggeri, B.A., Dionne, C.A., Vaught, J.L., Mallamo, J.P., Hudkins, R.L. J. Med. Chem. (2003) [Pubmed]
  25. Vascular endothelial growth factor stimulates embryonic urinary bladder development in organ culture. Burgu, B., McCarthy, L.S., Shah, V., Long, D.A., Wilcox, D.T., Woolf, A.S. BJU Int. (2006) [Pubmed]
  26. Estrogen regulates the production of VEGF for osteoclast formation and activity in op/op mice. Kodama, I., Niida, S., Sanada, M., Yoshiko, Y., Tsuda, M., Maeda, N., Ohama, K. J. Bone Miner. Res. (2004) [Pubmed]
  27. Placental defects in ARNT-knockout conceptus correlate with localized decreases in VEGF-R2, Ang-1, and Tie-2. Abbott, B.D., Buckalew, A.R. Dev. Dyn. (2000) [Pubmed]
  28. VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. Cursiefen, C., Chen, L., Borges, L.P., Jackson, D., Cao, J., Radziejewski, C., D'Amore, P.A., Dana, M.R., Wiegand, S.J., Streilein, J.W. J. Clin. Invest. (2004) [Pubmed]
  29. The second immunoglobulin-like domain of the VEGF tyrosine kinase receptor Flt-1 determines ligand binding and may initiate a signal transduction cascade. Davis-Smyth, T., Chen, H., Park, J., Presta, L.G., Ferrara, N. EMBO J. (1996) [Pubmed]
  30. Gene transfer of the vascular endothelial growth factor receptor flt-1 suppresses pulmonary metastasis associated with lung growth. Mae, M., O'Connor, T.P., Crystal, R.G. Am. J. Respir. Cell Mol. Biol. (2005) [Pubmed]
  31. Essential role of vascular endothelial growth factor in angiotensin II-induced vascular inflammation and remodeling. Zhao, Q., Ishibashi, M., Hiasa, K., Tan, C., Takeshita, A., Egashira, K. Hypertension (2004) [Pubmed]
  32. 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]
  33. Vascular endothelial growth factor A (VEGF-A) is involved in guidance of VEGF receptor-positive cells to the anterior portion of early embryos. Hiratsuka, S., Kataoka, Y., Nakao, K., Nakamura, K., Morikawa, S., Tanaka, S., Katsuki, M., Maru, Y., Shibuya, M. Mol. Cell. Biol. (2005) [Pubmed]
  34. AMG 706, an Oral, Multikinase Inhibitor that Selectively Targets Vascular Endothelial Growth Factor, Platelet-Derived Growth Factor, and Kit Receptors, Potently Inhibits Angiogenesis and Induces Regression in Tumor Xenografts. Polverino, A., Coxon, A., Starnes, C., Diaz, Z., Demelfi, T., Wang, L., Bready, J., Estrada, J., Cattley, R., Kaufman, S., Chen, D., Gan, Y., Kumar, G., Meyer, J., Neervannan, S., Alva, G., Talvenheimo, J., Montestruque, S., Tasker, A., Patel, V., Radinsky, R., Kendall, R. Cancer Res. (2006) [Pubmed]
  35. Suppression of ovarian cancer by muscle-mediated expression of soluble VEGFR-1/Flt-1 using adeno-associated virus serotype 1-derived vector. Takei, Y., Mizukami, H., Saga, Y., Yoshimura, I., Hasumi, Y., Takayama, T., Kohno, T., Matsushita, T., Okada, T., Kume, A., Suzuki, M., Ozawa, K. Int. J. Cancer (2007) [Pubmed]
  36. Ischemic preconditioning-mediated cardioprotection is disrupted in heterozygous Flt-1 (VEGFR-1) knockout mice. Addya, S., Shiroto, K., Turoczi, T., Zhan, L., Kaga, S., Fukuda, S., Surrey, S., Duan, L.J., Fong, G.H., Yamamoto, F., Maulik, N. J. Mol. Cell. Cardiol. (2005) [Pubmed]
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