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Gene Review

Fgfr2  -  fibroblast growth factor receptor 2

Mus musculus

Synonyms: AU043015, AW556123, Bek, Ect1, FGFR-2, ...
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Disease relevance of Fgfr2


High impact information on Fgfr2

  • To reveal the structural basis by which alternative splicing modulates the organizing activity of FGF8, we solved the crystal structure of FGF8b in complex with the "c" splice isoform of FGF receptor 2 (FGFR2c) [5].
  • The signaling pathways between endoderm-derived gastric epithelium and the surrounding mesenchyme are largely unknown; however, the developmental expression profile of the IIIb isoform of Fgfr2 (Fgfr2b) and its main ligand, Fgf10, suggest that they may be strong candidates [6].
  • Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation [7].
  • Activating mutations in fibroblast growth factor receptor 2 (FGFR2) cause several craniosynostosis syndromes by affecting the proliferation and differentiation of osteoblasts, which form the calvarial bones [7].
  • We analyzed the gene expression profiles of osteoblasts expressing FGFR2 activating mutations (C342Y or S252W) and found a striking down-regulation of the expression of many Wnt target genes and a concomitant induction of the transcription factor Sox2 [7].

Chemical compound and disease context of Fgfr2


Biological context of Fgfr2

  • Using a positional cloning approach, we identified the svs mutant lesion as a 491 bp insertion in the tenth intron of Fgfr2 that results in changes in the pattern of Fgfr2 alternative splicing [12].
  • An engineered null allele of Fgfr2 failed to complement the svs mutation proving that a partial loss of FGFR2(IIIb) isoforms causes svs phenotypes [12].
  • Fgfr2 is expressed only in proliferating osteoprogenitor cells; the onset of differentiation is preceded by down-regulation of Fgfr2 and up-regulation of Fgfr1 [13].
  • At early stages of embryogenesis, Fgfr1, Fgfr2, and several FGFs are critical for both the induction of the otic vesicle and the initial development of the sensory epithelium [14].
  • Using conditional gene ablation with the Cre-LoxP system in mice, we demonstrate a tissue-specific requirement for FGFR2 in urogenital epithelial cells - the precursors of prostatic epithelial cells - for prostatic branching morphogenesis and prostatic growth [15].

Anatomical context of Fgfr2

  • The epithelial b variant of Fgfr2 is active in the entire surface ectoderm of the early embryo, and later in the limb ectoderm and AER, where it is required for limb outgrowth [16].
  • As limb buds do not form in the absence of Fgfr2, we used chimera analysis to investigate the mechanism of action of this receptor in limb development [16].
  • The genes for the fibroblast growth factor receptors Fgfr2, Fgfr3, and Fgfr4 have been mapped in the mouse using an interspecific backcross mapping panel [17].
  • Twist is expressed in the midsutural mesenchyme and is partially co-expressed with Fgfr2, consistent with the possibility that it is involved in maintaining proliferation through regulating transcription of Fgfr2 [18].
  • We showed that murine FGFR2 is essential for chorioallantoic fusion and placenta trophoblast cell proliferation [19].

Associations of Fgfr2 with chemical compounds


Physical interactions of Fgfr2


Regulatory relationships of Fgfr2


Other interactions of Fgfr2

  • Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction [19].
  • We suggest that Fgfr2 is required for AER differentiation, as well as for En1 and Wnt7a expression [16].
  • High affinity binding of KGF was acquired only when also domain 2 in this chimera was replaced by its homologous domain from FGFR2 [27].
  • Finally, the intense expression of FGFR1 in odontoblasts and ameloblasts and FGFR2 IIIb in ameloblasts suggests that FGFs participate in regulation of their differentiation and/or secretory functions [23].
  • To explore functions of FGF/FGFR2 signals in development, we have mutated FGFR2 by deleting the entire immunoglobin-like domain III of the receptor [19].

Analytical, diagnostic and therapeutic context of Fgfr2

  • Using the yeast two-hybrid assay, we have identified ribosomal S6 kinase (RSK) to be a protein that associates with the cytoplasmic domain of the KGFR [28].
  • Our results provided significant insight into the mechanism of KGFR tumor suppression and suggest that KGFR gene therapy might be a viable method of inhibiting human salivary adenocarcinoma growth [29].
  • With in situ hybridization, predominantly the smooth muscle cells of large vessels expressed FGFR1 and 4 mRNA; the epithelial cells of large airways expressed FGFR1, 2, and 4; and alveolar cells expressed FGFR2, 3, and 4 [30].
  • Following the initial screening of hybridoma clones with a fluorescence-based, confocal cell detection method and ELISA, KGFR-specific MAbs were selected and confirmed by flow cytometry and Western blot analyses [31].
  • In this study, we generated murine MAbs specific to KGFR in non-obese diabetic (NOD) mice using a modified Repeated Immunizations at Multiple Sites (RIMMS) technology [31].


  1. Development of the mammalian urethra is controlled by Fgfr2-IIIb. Petiot, A., Perriton, C.L., Dickson, C., Cohn, M.J. Development (2005) [Pubmed]
  2. Mutations in fibroblast growth factor receptor 2 and fibroblast growth factor receptor 3 genes associated with human gastric and colorectal cancers. Jang, J.H., Shin, K.H., Park, J.G. Cancer Res. (2001) [Pubmed]
  3. Conditional inactivation of FGF receptor 2 reveals an essential role for FGF signaling in the regulation of osteoblast function and bone growth. Yu, K., Xu, J., Liu, Z., Sosic, D., Shao, J., Olson, E.N., Towler, D.A., Ornitz, D.M. Development (2003) [Pubmed]
  4. Loss of fibroblast growth factor receptor 2 ligand-binding specificity in Apert syndrome. Yu, K., Herr, A.B., Waksman, G., Ornitz, D.M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  5. Structural basis by which alternative splicing modulates the organizer activity of FGF8 in the brain. Olsen, S.K., Li, J.Y., Bromleigh, C., Eliseenkova, A.V., Ibrahimi, O.A., Lao, Z., Zhang, F., Linhardt, R.J., Joyner, A.L., Mohammadi, M. Genes Dev. (2006) [Pubmed]
  6. Stomach development is dependent on fibroblast growth factor 10/fibroblast growth factor receptor 2b-mediated signaling. Spencer-Dene, B., Sala, F.G., Bellusci, S., Gschmeissner, S., Stamp, G., Dickson, C. Gastroenterology (2006) [Pubmed]
  7. Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation. Mansukhani, A., Ambrosetti, D., Holmes, G., Cornivelli, L., Basilico, C. J. Cell Biol. (2005) [Pubmed]
  8. 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]
  9. Alternative splicing of fibroblast growth factor receptor 2 (FGF-R2) in human prostate cancer. Carstens, R.P., Eaton, J.V., Krigman, H.R., Walther, P.J., Garcia-Blanco, M.A. Oncogene (1997) [Pubmed]
  10. Mutation associated with Crouzon syndrome causes ligand-independent dimerization and activation of FGF receptor-2. Mangasarian, K., Li, Y., Mansukhani, A., Basilico, C. J. Cell. Physiol. (1997) [Pubmed]
  11. Link between reduced nephron number and hypertension: studies in a mutant mouse model. Poladia, D.P., Kish, K., Kutay, B., Bauer, J., Baum, M., Bates, C.M. Pediatr. Res. (2006) [Pubmed]
  12. The mouse seminal vesicle shape mutation is allelic with Fgfr2. Kuslak, S.L., Thielen, J.L., Marker, P.C. Development (2007) [Pubmed]
  13. 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]
  14. 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]
  15. Fibroblast growth factor receptor 2 tyrosine kinase is required for prostatic morphogenesis and the acquisition of strict androgen dependency for adult tissue homeostasis. Lin, Y., Liu, G., Zhang, Y., Hu, Y.P., Yu, K., Lin, C., McKeehan, K., Xuan, J.W., Ornitz, D.M., Shen, M.M., Greenberg, N., McKeehan, W.L., Wang, F. Development (2007) [Pubmed]
  16. Novel roles of Fgfr2 in AER differentiation and positioning of the dorsoventral limb interface. Gorivodsky, M., Lonai, P. Development (2003) [Pubmed]
  17. Mapping of murine fibroblast growth factor receptors refines regions of homology between mouse and human chromosomes. Avraham, K.B., Givol, D., Avivi, A., Yayon, A., Copeland, N.G., Jenkins, N.A. Genomics (1994) [Pubmed]
  18. Genetic control of the cell proliferation-differentiation balance in the developing skull vault: roles of fibroblast growth factor receptor signalling pathways. Morriss-Kay, G.M., Iseki, S., Johnson, D. Novartis Found. Symp. (2001) [Pubmed]
  19. Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction. Xu, X., Weinstein, M., Li, C., Naski, M., Cohen, R.I., Ornitz, D.M., Leder, P., Deng, C. Development (1998) [Pubmed]
  20. A model for the pharmacological treatment of crouzon syndrome. Perlyn, C.A., Morriss-Kay, G., Darvann, T., Tenenbaum, M., Ornitz, D.M. Neurosurgery (2006) [Pubmed]
  21. Identification of fibroblast growth factor 9 (FGF9) as a high affinity, heparin dependent ligand for FGF receptors 3 and 2 but not for FGF receptors 1 and 4. Hecht, D., Zimmerman, N., Bedford, M., Avivi, A., Yayon, A. Growth Factors (1995) [Pubmed]
  22. Induction of urothelial cell proliferation by fibroblast growth factor-7 in RAG1-deficient mice. Bassuk, J.A., Cochrane, K., Mitchell, M.E. Adv. Exp. Med. Biol. (2003) [Pubmed]
  23. 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]
  24. MINT, the Msx2 interacting nuclear matrix target, enhances Runx2-dependent activation of the osteocalcin fibroblast growth factor response element. Sierra, O.L., Cheng, S.L., Loewy, A.P., Charlton-Kachigian, N., Towler, D.A. J. Biol. Chem. (2004) [Pubmed]
  25. FGF3 attached to a phosholipid membrane anchor gains a high transforming capacity. Implications of microdomains for FGF3 cell transformation. Köhl, R., Antoine, M., Reimers, K., Kiefer, P. J. Biol. Chem. (2002) [Pubmed]
  26. Regulation of FGF receptor-2 expression by transcription factor E2F-1. Tashiro, E., Minato, Y., Maruki, H., Asagiri, M., Imoto, M. Oncogene (2003) [Pubmed]
  27. Multiple structural elements determine ligand binding of fibroblast growth factor receptors. Evidence that both Ig domain 2 and 3 define receptor specificity. Zimmer, Y., Givol, D., Yayon, A. J. Biol. Chem. (1993) [Pubmed]
  28. Ribosomal S6 kinase as a mediator of keratinocyte growth factor-induced activation of Akt in epithelial cells. Pan, Z.Z., Devaux, Y., Ray, P. Mol. Biol. Cell (2004) [Pubmed]
  29. Growth inhibition by keratinocyte growth factor receptor of human salivary adenocarcinoma cells through induction of differentiation and apoptosis. Zhang, Y., Wang, H., Toratani, S., Sato, J.D., Kan, M., McKeehan, W.L., Okamoto, T. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  30. Differential expression of fibroblast growth factor receptors 1 to 4 and ligand genes in late fetal and early postnatal rat lung. Powell, P.P., Wang, C.C., Horinouchi, H., Shepherd, K., Jacobson, M., Lipson, M., Jones, R. Am. J. Respir. Cell Mol. Biol. (1998) [Pubmed]
  31. Generation and characterization of monoclonal antibodies to human keratinocyte growth factor receptor. Wei, P., Zhan, J., Liu, S., Chang, D., Haldankar, R., Burkhardt, K., Crouse, J., Hui, J., Juan, T., Talvenheimo, J., Kim, H., Li, L., Boone, T., Borges, L. Hybridoma (2005) (2006) [Pubmed]
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