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Gene Review

Fgfr1  -  fibroblast growth factor receptor 1

Mus musculus

Synonyms: AW208770, Basic fibroblast growth factor receptor 1, Eask, FGFR-1, FLG, ...
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Disease relevance of Fgfr1

  • Here we show that mice carrying a Pro250Arg mutation in Fgfr1, which is orthologous to the Pfeiffer syndrome mutation in humans, exhibit anterio-posteriorly shortened, laterally widened and vertically heightened neurocraniums [1].
  • First, we employed the aphakia (ak) lens complementation system to show that Fgfr1 deficient embryonic stem (ES) cells were able to form a normal embryonic lens that maintains a normal pattern of crystallin gene expression [2].
  • Development of the geniculate placode as well as the VIIth cranial ganglion is affected in Fgfr1 hypomorphs [3].
  • Although FGFR1 is expressed by hepatic cell progenitors and adult nonparenchymal cells, ectopic expression is commonly observed in hepatoma cells [4].
  • However, in diethylnitrosamine-treated mice, the chronic FGFR1 activity promoted an incidence of 44% adenomas at 4 months and 38% hepatocellular carcinoma at 8 months [4].

Psychiatry related information on Fgfr1


High impact information on Fgfr1


Chemical compound and disease context of Fgfr1


Biological context of Fgfr1


Anatomical context of Fgfr1

  • We show that Cre-mediated deletion of Fgfr1 in limb mesenchyme, beginning at a time point slightly after the first sign of initial budding, primarily affects formation of the first one or two digits [22].
  • In the Fgfr1-deficient telencephalon, AP patterning is largely normal [17].
  • Chimeric analysis of fibroblast growth factor receptor-1 (Fgfr1) function: a role for FGFR1 in morphogenetic movement through the primitive streak [23].
  • Mice lacking Fgfr1, either in progenitor cells or in differentiated osteoblasts, showed increased bone mass as adults [24].
  • To investigate the biological basis of FGFR signalling pathways in the developing calvarium we compared the expression patterns of Twist with those of Fgfr1, -2 and -3 in the fetal mouse coronal suture over the course of embryonic days 14-18, as the suture is initiated and matures [21].

Associations of Fgfr1 with chemical compounds


Physical interactions of Fgfr1

  • To determine the developmental requirements for Fgfr1-Frs signaling, we generated mice (Fgfr1(Delta)Frs/DeltaFrs) in which the Frs2/3-binding site on Fgfr1 is deleted [31].
  • Despite the fact that we have observed inhibition of bFGF binding by the 18-mer phosphorothioate oligodeoxynucleotides for both the high and low affinity classes of bFGF receptor, the inhibition was sequence-selective only for the high affinity receptors [32].
  • We have also demonstrated that a monoclonal antibody prepared against FGF receptor (R)-1 is able to co-precipitate Src-related proteins in lysates from FGF-1-treated NIH 3T3 cells [33].
  • Using a receptor binding competition assay, Fgf3 was shown to bind with high affinity to the IIIb isoforms of Fgf receptor (FgfR) 1 and FgfR2 (ID50 = approximately 0.8 nM) and with a lower affinity to the IIIc variant of FgfR2 (ID50 = approximately 9 nM) [34].
  • FGF-23 binds to the FGF receptor 3c, which is mainly expressed in opossum kidney cells, with high affinity [35].

Enzymatic interactions of Fgfr1


Regulatory relationships of Fgfr1


Other interactions of Fgfr1

  • We show that FGF signals promote coronary growth indirectly by signaling to the cardiomyoblast through redundant function of Fgfr1 and Fgfr2 [41].
  • These data demonstrate that FGF18 signals through another FGFR to regulate osteoblast growth [42].
  • Like FGFR1 and FGFR3, it exists as two splice variants, IIIb and IIIc [43].
  • An examination of fgf receptor gene expression indicated that all four receptors (fgfr-1 to fgfr-4) are expressed in postnatal lungs at varying levels [44].
  • As Bmp7 is an established lens induction signal, this provides further evidence that Fgfr activity is important for lens induction [45].

Analytical, diagnostic and therapeutic context of Fgfr1


  1. A Pro250Arg substitution in mouse Fgfr1 causes increased expression of Cbfa1 and premature fusion of calvarial sutures. Zhou, Y.X., Xu, X., Chen, L., Li, C., Brodie, S.G., Deng, C.X. Hum. Mol. Genet. (2000) [Pubmed]
  2. Fibroblast growth factor receptor 1 (Fgfr1) is not essential for lens fiber differentiation in mice. Zhao, H., Yang, Y., Partanen, J., Ciruna, B.G., Rossant, J., Robinson, M.L. Mol. Vis. (2006) [Pubmed]
  3. Fibroblast growth factor signalling and regional specification of the pharyngeal ectoderm. Trokovic, N., Trokovic, R., Partanen, J. Int. J. Dev. Biol. (2005) [Pubmed]
  4. Ectopic activity of fibroblast growth factor receptor 1 in hepatocytes accelerates hepatocarcinogenesis by driving proliferation and vascular endothelial growth factor-induced angiogenesis. Huang, X., Yu, C., Jin, C., Kobayashi, M., Bowles, C.A., Wang, F., McKeehan, W.L. Cancer Res. (2006) [Pubmed]
  5. The pleiotropic effects of fibroblast growth factor receptors in mammalian development. McIntosh, I., Bellus, G.A., Jab, E.W. Cell Struct. Funct. (2000) [Pubmed]
  6. Fibroblast growth factor receptor-1 expression in the cortex and hippocampus in Alzheimer's disease. Takami, K., Matsuo, A., Terai, K., Walker, D.G., McGeer, E.G., McGeer, P.L. Brain Res. (1998) [Pubmed]
  7. Diverse signaling pathways activated by growth factor receptors induce broadly overlapping, rather than independent, sets of genes. Fambrough, D., McClure, K., Kazlauskas, A., Lander, E.S. Cell (1999) [Pubmed]
  8. Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor. Yayon, A., Klagsbrun, M., Esko, J.D., Leder, P., Ornitz, D.M. Cell (1991) [Pubmed]
  9. Human fibroblast growth factor receptor 1 is a co-receptor for infection by adeno-associated virus 2. Qing, K., Mah, C., Hansen, J., Zhou, S., Dwarki, V., Srivastava, A. Nat. Med. (1999) [Pubmed]
  10. Antisense targeting of basic fibroblast growth factor and fibroblast growth factor receptor-1 in human melanomas blocks intratumoral angiogenesis and tumor growth. Wang, Y., Becker, D. Nat. Med. (1997) [Pubmed]
  11. Activation of Stat1 by mutant fibroblast growth-factor receptor in thanatophoric dysplasia type II dwarfism. Su, W.C., Kitagawa, M., Xue, N., Xie, B., Garofalo, S., Cho, J., Deng, C., Horton, W.A., Fu, X.Y. Nature (1997) [Pubmed]
  12. Inhibition of fibroblast growth factor/fibroblast growth factor receptor activity in glioma cells impedes tumor growth by both angiogenesis-dependent and -independent mechanisms. Auguste, P., Gürsel, D.B., Lemière, S., Reimers, D., Cuevas, P., Carceller, F., Di Santo, J.P., Bikfalvi, A. Cancer Res. (2001) [Pubmed]
  13. Chronic activity of ectopic type 1 fibroblast growth factor receptor tyrosine kinase in prostate epithelium results in hyperplasia accompanied by intraepithelial neoplasia. Wang, F., McKeehan, K., Yu, C., Ittmann, M., McKeehan, W.L. Prostate (2004) [Pubmed]
  14. Hepatocyte growth factor receptor is a coreceptor for adeno-associated virus type 2 infection. Kashiwakura, Y., Tamayose, K., Iwabuchi, K., Hirai, Y., Shimada, T., Matsumoto, K., Nakamura, T., Watanabe, M., Oshimi, K., Daida, H. J. Virol. (2005) [Pubmed]
  15. Simultaneous induction of apoptosis, collagen type I expression and mineralization in the developing coronal suture following FGF4 and FGF2 application. Mathijssen, I.M., van Leeuwen, J.P., Vermeij-Keers, C. J. Craniofac. Genet. Dev. Biol. (2000) [Pubmed]
  16. Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. Rousseau, F., Bonaventure, J., Legeai-Mallet, L., Pelet, A., Rozet, J.M., Maroteaux, P., Le Merrer, M., Munnich, A. Nature (1994) [Pubmed]
  17. FGF signaling through FGFR1 is required for olfactory bulb morphogenesis. Hébert, J.M., Lin, M., Partanen, J., Rossant, J., McConnell, S.K. Development (2003) [Pubmed]
  18. Fgfr1 and Fgfr2 have distinct differentiation- and proliferation-related roles in the developing mouse skull vault. Iseki, S., Wilkie, A.O., Morriss-Kay, G.M. Development (1999) [Pubmed]
  19. Mutant analyses reveal different functions of fgfr1 in medaka and zebrafish despite conserved ligand-receptor relationships. Yokoi, H., Shimada, A., Carl, M., Takashima, S., Kobayashi, D., Narita, T., Jindo, T., Kimura, T., Kitagawa, T., Kage, T., Sawada, A., Naruse, K., Asakawa, S., Shimizu, N., Mitani, H., Shima, A., Tsutsumi, M., Hori, H., Wittbrodt, J., Saga, Y., Ishikawa, Y., Araki, K., Takeda, H. Dev. Biol. (2007) [Pubmed]
  20. Loss of Fgfr3 leads to excess hair cell development in the mouse organ of Corti. Hayashi, T., Cunningham, D., Bermingham-McDonogh, O. Dev. Dyn. (2007) [Pubmed]
  21. Expression patterns of Twist and Fgfr1, -2 and -3 in the developing mouse coronal suture suggest a key role for twist in suture initiation and biogenesis. Johnson, D., Iseki, S., Wilkie, A.O., Morriss-Kay, G.M. Mech. Dev. (2000) [Pubmed]
  22. FGFR1 function at the earliest stages of mouse limb development plays an indispensable role in subsequent autopod morphogenesis. Li, C., Xu, X., Nelson, D.K., Williams, T., Kuehn, M.R., Deng, C.X. Development (2005) [Pubmed]
  23. Chimeric analysis of fibroblast growth factor receptor-1 (Fgfr1) function: a role for FGFR1 in morphogenetic movement through the primitive streak. Ciruna, B.G., Schwartz, L., Harpal, K., Yamaguchi, T.P., Rossant, J. Development (1997) [Pubmed]
  24. Fibroblast growth factor receptor 1 signaling in the osteo-chondrogenic cell lineage regulates sequential steps of osteoblast maturation. Jacob, A.L., Smith, C., Partanen, J., Ornitz, D.M. Dev. Biol. (2006) [Pubmed]
  25. Gene expression profiles of mouse submandibular gland development: FGFR1 regulates branching morphogenesis in vitro through BMP- and FGF-dependent mechanisms. Hoffman, M.P., Kidder, B.L., Steinberg, Z.L., Lakhani, S., Ho, S., Kleinman, H.K., Larsen, M. Development (2002) [Pubmed]
  26. Interaction of androgen-induced autocrine heparin-binding growth factor with fibroblast growth factor receptor on androgen-dependent Shionogi carcinoma 115 cells. Nonomura, N., Lu, J., Tanaka, A., Yamanishi, H., Sato, B., Sonoda, T., Matsumoto, K. Cancer Res. (1990) [Pubmed]
  27. Intact and functional fibroblast growth factor (FGF) receptor-1 trafficks near the nucleus in response to FGF-1. Prudovsky, I., Savion, N., Zhan, X., Friesel, R., Xu, J., Hou, J., McKeehan, W.L., Maciag, T. J. Biol. Chem. (1994) [Pubmed]
  28. Androgen and fibroblast growth factor (FGF) regulation of FGF receptors in S115 mouse mammary tumor cells. Ruohola, J.K., Valve, E.M., Vainikka, S., Alitalo, K., Härkönen, P.L. Endocrinology (1995) [Pubmed]
  29. Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain. Mohammadi, M., Froum, S., Hamby, J.M., Schroeder, M.C., Panek, R.L., Lu, G.H., Eliseenkova, A.V., Green, D., Schlessinger, J., Hubbard, S.R. EMBO J. (1998) [Pubmed]
  30. Fibroblast growth factor receptor-1 is required for long-term potentiation, memory consolidation, and neurogenesis. Zhao, M., Li, D., Shimazu, K., Zhou, Y.X., Lu, B., Deng, C.X. Biol. Psychiatry (2007) [Pubmed]
  31. Context-specific requirements for Fgfr1 signaling through Frs2 and Frs3 during mouse development. Hoch, R.V., Soriano, P. Development (2006) [Pubmed]
  32. Phosphorothioate oligodeoxynucleotides bind to basic fibroblast growth factor, inhibit its binding to cell surface receptors, and remove it from low affinity binding sites on extracellular matrix. Guvakova, M.A., Yakubov, L.A., Vlodavsky, I., Tonkinson, J.L., Stein, C.A. J. Biol. Chem. (1995) [Pubmed]
  33. Association of fibroblast growth factor receptor-1 with c-Src correlates with association between c-Src and cortactin. Zhan, X., Plourde, C., Hu, X., Friesel, R., Maciag, T. J. Biol. Chem. (1994) [Pubmed]
  34. Receptor binding and mitogenic properties of mouse fibroblast growth factor 3. Modulation of response by heparin. Mathieu, M., Chatelain, E., Ornitz, D., Bresnick, J., Mason, I., Kiefer, P., Dickson, C. J. Biol. Chem. (1995) [Pubmed]
  35. Fibroblast growth factor (FGF)-23 inhibits renal phosphate reabsorption by activation of the mitogen-activated protein kinase pathway. Yamashita, T., Konishi, M., Miyake, A., Inui, K., Itoh, N. J. Biol. Chem. (2002) [Pubmed]
  36. Shp2, an SH2-containing protein-tyrosine phosphatase, positively regulates receptor tyrosine kinase signaling by dephosphorylating and inactivating the inhibitor Sprouty. Hanafusa, H., Torii, S., Yasunaga, T., Matsumoto, K., Nishida, E. J. Biol. Chem. (2004) [Pubmed]
  37. Responsiveness of developing dental tissues to fibroblast growth factors: expression of splicing alternatives of FGFR1, -2, -3, and of FGFR4; and stimulation of cell proliferation by FGF-2, -4, -8, and -9. Kettunen, P., Karavanova, I., Thesleff, I. Dev. Genet. (1998) [Pubmed]
  38. N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor signalling. Cavallaro, U., Niedermeyer, J., Fuxa, M., Christofori, G. Nat. Cell Biol. (2001) [Pubmed]
  39. Suramin interrupts androgen-inducible autocrine loop involving heparin binding growth factor in mouse mammary cancer (Shionogi carcinoma 115) cells. Kasayama, S., Saito, H., Kouhara, H., Sumitani, S., Sato, B. J. Cell. Physiol. (1993) [Pubmed]
  40. Differentially expressed fibroblast growth factors regulate skeletal muscle development through autocrine and paracrine mechanisms. Hannon, K., Kudla, A.J., McAvoy, M.J., Clase, K.L., Olwin, B.B. J. Cell Biol. (1996) [Pubmed]
  41. Fibroblast growth factor signals regulate a wave of Hedgehog activation that is essential for coronary vascular development. Lavine, K.J., White, A.C., Park, C., Smith, C.S., Choi, K., Long, F., Hui, C.C., Ornitz, D.M. Genes Dev. (2006) [Pubmed]
  42. Coordination of chondrogenesis and osteogenesis by fibroblast growth factor 18. Liu, Z., Xu, J., Colvin, J.S., Ornitz, D.M. Genes Dev. (2002) [Pubmed]
  43. The IIIc alternative of Fgfr2 is a positive regulator of bone formation. Eswarakumar, V.P., Monsonego-Ornan, E., Pines, M., Antonopoulou, I., Morriss-Kay, G.M., Lonai, P. Development (2002) [Pubmed]
  44. FGFR-3 and FGFR-4 function cooperatively to direct alveogenesis in the murine lung. Weinstein, M., Xu, X., Ohyama, K., Deng, C.X. Development (1998) [Pubmed]
  45. Fgf receptor signaling plays a role in lens induction. Faber, S.C., Dimanlig, P., Makarenkova, H.P., Shirke, S., Ko, K., Lang, R.A. Development (2001) [Pubmed]
  46. A functional fibroblast growth factor-1 immunoglobulin fusion protein. Dikov, M.M., Reich, M.B., Dworkin, L., Thomas, J.W., Miller, G.G. J. Biol. Chem. (1998) [Pubmed]
  47. Expression of the fibroblast growth factor receptor FGFR-1/flg during gastrulation and segmentation in the mouse embryo. Yamaguchi, T.P., Conlon, R.A., Rossant, J. Dev. Biol. (1992) [Pubmed]
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