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Gene Review

FGFR2  -  fibroblast growth factor receptor 2

Homo sapiens

Synonyms: BBDS, BEK, BFR-1, CD332, CEK3, ...
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Disease relevance of FGFR2


High impact information on FGFR2

  • Interestingly, this common mutation occurs precisely at the analogous position within the FGFR3 protein as the mutations in FGFR1 (Pro252Arg) and FGFR2 (Pro253Arg) previously reported in Pfeiffer and Apert syndromes, respectively [5].
  • Apert syndrome results from one or other of two specific nucleotide substitutions, both C-->G transversions, in the fibroblast growth factor receptor 2 (FGFR2) gene [6].
  • The gene on chromosome 10 is FGFR2 with several different mutations causing sporadic and familial PS (Table 1) [5].
  • FGFR2 mutations in Pfeiffer syndrome [7].
  • Identical mutations in the FGFR2 gene cause both Pfeiffer and Crouzon syndrome phenotypes [8].

Chemical compound and disease context of FGFR2


Biological context of FGFR2


Anatomical context of FGFR2

  • Furthermore, the expression of the high-affinity receptor tyrosine kinase to KGF (FGFR2) is predominantly detectable in alpha2beta1(hi) CD133- TAP cells when compared with stem cells (alpha2beta1(hi) CD133+), which would therefore be relatively unresponsive to the differentiating effect of KGF [17].
  • Thus, by mimicking the paracrine pathway (on proliferation, growth in soft agar and invasion) on the human prostatic epithelial cell line PNT1A positively checked for FGFR2/IIIb expression, FGF7 significantly enhanced cell proliferation at an optimal concentration of 7.5 x 10(-11) M, but no significant invasion or growth in soft agar were observed [18].
  • In an in vitro control model of calvarial osteoblasts from Apert patients carrying the FGFR2 P253R mutation, we studied the changes in cellular phenotype and evaluated the effects of FGF2 [19].
  • Reverse transcription-polymerase chain reaction and Southern blot transfer of mRNA derived from 7 SCCHN cell lines showed that the IIIb isoform of FGF-receptor 2 (FGFR2) was expressed at high levels, whereas the IIIc isoform and FGFRI were weakly expressed or not detected [20].
  • Widespread co-expression of FGFR1 and FGFR2 was observed in intimal smooth muscle cells, foam cells and the plaque microvasculature of simple and advanced lesions [21].

Associations of FGFR2 with chemical compounds

  • Here we report the crystal structure of the FGFR2 ectodomain in a dimeric form that is induced by simultaneous binding to FGF1 and a heparin decasaccharide [22].
  • Mutations in FGFR2 clustered at two critical cysteine residues, 278 and 342, which were involved in 18 of 30 cases (60%) [23].
  • H16N2 cells expressing the full-length FGFR2 with the C1 or C3 carboxyl terminus were tested for their ability to grow under epidermal growth factor (EGF)-independent conditions, in soft agar, and for their ability to invade naturally occurring basement membranes and compared with the parental SUM-52PE cell line [24].
  • Phosphorylation of the adapter protein FGF receptor substrate 2 is much more robust in the cells expressing the C3 variant of FGFR2 compared with the C1 variant [24].
  • These PCSCs possessed estrogen receptors and KGFR, but not androgen receptor as determined by RT-PCR and Western blot, respectively [25].

Physical interactions of FGFR2


Co-localisations of FGFR2


Regulatory relationships of FGFR2


Other interactions of FGFR2

  • We have crystallized a complex between human FGF1 and a two-domain extracellular fragment of human FGFR2 [34].
  • By prior convention, the previously reported from of FGFR3 was designated IIIc due to its high degree of homology with the IIIc domain of FGFR1 (83% homology) and the IIIc domain of FGFR2 (81% homology) [35].
  • FGFR1, FGFR2 and FGFR4 were expressed at high levels in respectively 22%, 4% and 32% of tumors [36].
  • The sequence variations c.590C>G and c.582-62G>A in FGF8, and, c.550+27C>T, c.727+180T>G, c.830T>C (p.Me186Thr), and c.2454C>T in FGFR2 were found uniquely in patients with hypospadias, as compared with 96 controls [37].
  • During the subsequent development and commitment of the melanoblast, concomitant expression of the receptors for fibroblasts growth factor (FGFR2), endothelin-B (EDNRB), and steel factor (cKIT) also appears essential for the continued survival of migrating melanoblasts [38].
  • Reexpression of FGFR2 competes with FGFR1 for the immediate substrate FGFR substrate 2 to impede signaling upstream of the BRAF/MAPK pathway [39].

Analytical, diagnostic and therapeutic context of FGFR2


  1. Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans. Meyers, G.A., Orlow, S.J., Munro, I.R., Przylepa, K.A., Jabs, E.W. Nat. Genet. (1995) [Pubmed]
  2. Biochemical analysis of pathogenic ligand-dependent FGFR2 mutations suggests distinct pathophysiological mechanisms for craniofacial and limb abnormalities. Ibrahimi, O.A., Zhang, F., Eliseenkova, A.V., Itoh, N., Linhardt, R.J., Mohammadi, M. Hum. Mol. Genet. (2004) [Pubmed]
  3. Analysis of the mutational spectrum of the FGFR2 gene in Pfeiffer syndrome. Cornejo-Roldan, L.R., Roessler, E., Muenke, M. Hum. Genet. (1999) [Pubmed]
  4. Evaluation of the fibroblast growth factor system as a potential target for therapy in human prostate cancer. Gowardhan, B., Douglas, D.A., Mathers, M.E., McKie, A.B., McCracken, S.R., Robson, C.N., Leung, H.Y. Br. J. Cancer (2005) [Pubmed]
  5. Identical mutations in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes. Bellus, G.A., Gaudenz, K., Zackai, E.H., Clarke, L.A., Szabo, J., Francomano, C.A., Muenke, M. Nat. Genet. (1996) [Pubmed]
  6. Exclusive paternal origin of new mutations in Apert syndrome. Moloney, D.M., Slaney, S.F., Oldridge, M., Wall, S.A., Sahlin, P., Stenman, G., Wilkie, A.O. Nat. Genet. (1996) [Pubmed]
  7. FGFR2 mutations in Pfeiffer syndrome. Lajeunie, E., Ma, H.W., Bonaventure, J., Munnich, A., Le Merrer, M., Renier, D. Nat. Genet. (1995) [Pubmed]
  8. Identical mutations in the FGFR2 gene cause both Pfeiffer and Crouzon syndrome phenotypes. Rutland, P., Pulleyn, L.J., Reardon, W., Baraitser, M., Hayward, R., Jones, B., Malcolm, S., Winter, R.M., Oldridge, M., Slaney, S.F. Nat. Genet. (1995) [Pubmed]
  9. Differential signal transduction of alternatively spliced FGFR2 variants expressed in human mammary epithelial cells. Moffa, A.B., Ethier, S.P. J. Cell. Physiol. (2007) [Pubmed]
  10. Trp290Cys mutation in exon IIIa of the fibroblast growth factor receptor 2 (FGFR2) gene is associated with Pfeiffer syndrome. Tartaglia, M., Valeri, S., Velardi, F., Di Rocco, C., Battaglia, P.A. Hum. Genet. (1997) [Pubmed]
  11. A soluble form of K-sam/FGFR2 protein in the culture medium of human gastric cancer cells. Kishi, T., Yoshida, T., Terada, M. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  12. A Novel Molecular Targeting Compound as K-samII/FGF-R2 Phosphorylation Inhibitor, Ki23057, for Scirrhous Gastric Cancer. Nakamura, K., Yashiro, M., Matsuoka, T., Tendo, M., Shimizu, T., Miwa, A., Hirakawa, K. Gastroenterology (2006) [Pubmed]
  13. Estrogen receptor-associated expression of keratinocyte growth factor and its possible role in the inhibition of apoptosis in human breast cancer. Tamaru, N., Hishikawa, Y., Ejima, K., Nagasue, N., Inoue, S., Muramatsu, M., Hayashi, T., Koji, T. Lab. Invest. (2004) [Pubmed]
  14. Genomic screening of fibroblast growth-factor receptor 2 reveals a wide spectrum of mutations in patients with syndromic craniosynostosis. Kan, S.H., Elanko, N., Johnson, D., Cornejo-Roldan, L., Cook, J., Reich, E.W., Tomkins, S., Verloes, A., Twigg, S.R., Rannan-Eliya, S., McDonald-McGinn, D.M., Zackai, E.H., Wall, S.A., Muenke, M., Wilkie, A.O. Am. J. Hum. Genet. (2002) [Pubmed]
  15. Cellular signaling by fibroblast growth factor receptors. Eswarakumar, V.P., Lax, I., Schlessinger, J. Cytokine Growth Factor Rev. (2005) [Pubmed]
  16. Different abilities of the four FGFRs to mediate FGF-1 translocation are linked to differences in the receptor C-terminal tail. S??rensen, V., Wiedlocha, A., Haugsten, E.M., Khnykin, D., Wesche, J., Olsnes, S. J. Cell. Sci. (2006) [Pubmed]
  17. KGF suppresses alpha2beta1 integrin function and promotes differentiation of the transient amplifying population in human prostatic epithelium. Heer, R., Collins, A.T., Robson, C.N., Shenton, B.K., Leung, H.Y. J. Cell. Sci. (2006) [Pubmed]
  18. FGF7/KGF triggers cell transformation and invasion on immortalised human prostatic epithelial PNT1A cells. Ropiquet, F., Huguenin, S., Villette, J.M., Ronflé, V., Le Brun, G., Maitland, N.J., Cussenot, O., Fiet, J., Berthon, P. Int. J. Cancer (1999) [Pubmed]
  19. P253R fibroblast growth factor receptor-2 mutation induces RUNX2 transcript variants and calvarial osteoblast differentiation. Baroni, T., Carinci, P., Lilli, C., Bellucci, C., Aisa, M.C., Scapoli, L., Volinia, S., Carinci, F., Pezzetti, F., Calvitti, M., Farina, A., Conte, C., Bodo, M. J. Cell. Physiol. (2005) [Pubmed]
  20. Expression of basic fibroblast growth factor in squamous cell carcinoma of the head and neck is associated with degree of histologic differentiation. Janot, F., el-Naggar, A.K., Morrison, R.S., Liu, T.J., Taylor, D.L., Clayman, G.L. Int. J. Cancer (1995) [Pubmed]
  21. Localisation and differential expression of the fibroblast growth factor receptor (FGFR) multigene family in normal and atherosclerotic human arteries. Hughes, S.E. Cardiovasc. Res. (1996) [Pubmed]
  22. Crystal structure of fibroblast growth factor receptor ectodomain bound to ligand and heparin. Pellegrini, L., Burke, D.F., von Delft, F., Mulloy, B., Blundell, T.L. Nature (2000) [Pubmed]
  23. Clustering of FGFR2 gene mutations inpatients with Pfeiffer and Crouzon syndromes (FGFR2-associated craniosynostoses). Kress, W., Collmann, H., Büsse, M., Halliger-Keller, B., Mueller, C.R. Cytogenet. Cell Genet. (2000) [Pubmed]
  24. Transforming potential of alternatively spliced variants of fibroblast growth factor receptor 2 in human mammary epithelial cells. Moffa, A.B., Tannheimer, S.L., Ethier, S.P. Mol. Cancer Res. (2004) [Pubmed]
  25. Effect of keratinocyte growth factor on cell viability in primary cultured human prostate cancer stromal cells. Huang, Y.W., Wang, L.S., Chang, H.L., Ye, W., Shu, S., Sugimoto, Y., Lin, Y.C. J. Steroid Biochem. Mol. Biol. (2006) [Pubmed]
  26. The cytoplasmic tyrosine kinase Pyk2 as a novel effector of fibroblast growth factor receptor 3 activation. Meyer, A.N., Gastwirt, R.F., Schlaepfer, D.D., Donoghue, D.J. J. Biol. Chem. (2004) [Pubmed]
  27. A role for fibroblast growth factor receptor-2 in the altered osteoblast phenotype induced by Twist haploinsufficiency in the Saethre-Chotzen syndrome. Guenou, H., Kaabeche, K., Mée, S.L., Marie, P.J. Hum. Mol. Genet. (2005) [Pubmed]
  28. Heparin differentially regulates the interaction of fibroblast growth factor-4 with FGF receptors 1 and 2. Aviezer, D., Safran, M., Yayon, A. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  29. Keratinocyte growth factor receptor expression in normal colorectal epithelial cells and differentiated type of colorectal cancer. Yoshino, M., Ishiwata, T., Watanabe, M., Komine, O., Shibuya, T., Tokunaga, A., Naito, Z. Oncol. Rep. (2005) [Pubmed]
  30. Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors. Yeh, B.K., Igarashi, M., Eliseenkova, A.V., Plotnikov, A.N., Sher, I., Ron, D., Aaronson, S.A., Mohammadi, M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  31. Fibroblast growth factors and their receptors in parathyroid disease. Lambert, D., Eaton, C.L., Harrison, B.J. World journal of surgery. (1998) [Pubmed]
  32. Role of keratinocyte growth factor in the pathogenesis of autosomal dominant polycystic kidney disease. Mei, C., Mao, Z., Shen, X., Wang, W., Dai, B., Tang, B., Wu, Y., Cao, Y., Zhang, S., Zhao, H., Sun, T. Nephrol. Dial. Transplant. (2005) [Pubmed]
  33. Cbl-mediated ubiquitination of alpha5 integrin subunit mediates fibronectin-dependent osteoblast detachment and apoptosis induced by FGFR2 activation. Kaabeche, K., Guenou, H., Bouvard, D., Didelot, N., Listrat, A., Marie, P.J. J. Cell. Sci. (2005) [Pubmed]
  34. Structural interactions of fibroblast growth factor receptor with its ligands. Stauber, D.J., DiGabriele, A.D., Hendrickson, W.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  35. Identification of a novel variant form of fibroblast growth factor receptor 3 (FGFR3 IIIb) in human colonic epithelium. Murgue, B., Tsunekawa, S., Rosenberg, I., deBeaumont, M., Podolsky, D.K. Cancer Res. (1994) [Pubmed]
  36. Expression of FGF and FGF receptor genes in human breast cancer. Penault-Llorca, F., Bertucci, F., Adélaïde, J., Parc, P., Coulier, F., Jacquemier, J., Birnbaum, D., deLapeyrière, O. Int. J. Cancer (1995) [Pubmed]
  37. FGFR2, FGF8, FGF10 and BMP7 as candidate genes for hypospadias. Beleza-Meireles, A., Lundberg, F., Lagerstedt, K., Zhou, X., Omrani, D., Frisén, L., Nordenskjöld, A. Eur. J. Hum. Genet. (2007) [Pubmed]
  38. Molecular basis of congenital hypopigmentary disorders in humans: a review. Boissy, R.E., Nordlund, J.J. Pigment Cell Res. (1997) [Pubmed]
  39. Epigenetically controlled fibroblast growth factor receptor 2 signaling imposes on the RAS/BRAF/mitogen-activated protein kinase pathway to modulate thyroid cancer progression. Kondo, T., Zheng, L., Liu, W., Kurebayashi, J., Asa, S.L., Ezzat, S. Cancer Res. (2007) [Pubmed]
  40. Expression of basic fibroblast growth factor and its receptors FGFR1 and FGFR2 in human benign prostatic hyperplasia treated with finasteride. Sáez, C., González-Baena, A.C., Japón, M.A., Giráldez, J., Segura, D.I., Rodríguez-Vallejo, J.M., González-Esteban, J., Miranda, G., Torrubia, F. Prostate (1999) [Pubmed]
  41. Expression of basic fibroblast growth factor (bFGF), FGF receptor 1 and FGF receptor 2 in uterine leiomyomas and myometrium during the menstrual cycle, after menopause and GnRHa treatment. Wu, X., Blanck, A., Olovsson, M., Möller, B., Lindblom, B. Acta obstetricia et gynecologica Scandinavica. (2001) [Pubmed]
  42. Differential expression of fibroblast growth factor receptors in human digital development suggests common pathogenesis in complex acrosyndactyly and craniosynostosis. Britto, J.A., Chan, J.C., Evans, R.D., Hayward, R.D., Jones, B.M. Plast. Reconstr. Surg. (2001) [Pubmed]
  43. p21-activated protein kinase 4 (PAK4) interacts with the keratinocyte growth factor receptor and participates in keratinocyte growth factor-mediated inhibition of oxidant-induced cell death. Lu, Y., Pan, Z.Z., Devaux, Y., Ray, P. J. Biol. Chem. (2003) [Pubmed]
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