fibroblast growth factor receptor 2


Gene Symbol: fibroblast growth factor receptor 2
Description: fibroblast growth factor receptor 2
Alias: fibroblast growth factor receptor 2
Species: rat

Top Publications

  1. Jaskoll T, Zhou Y, Chai Y, Makarenkova H, Collinson J, West J, et al. Embryonic submandibular gland morphogenesis: stage-specific protein localization of FGFs, BMPs, Pax6 and Pax9 in normal mice and abnormal SMG phenotypes in FgfR2-IIIc(+/Delta), BMP7(-/-) and Pax6(-/-) mice. Cells Tissues Organs. 2002;170:83-98 pubmed
    ..Finally, our observations of abnormal SMGs in BMP7(-/-) and Pax6(-/-) indicate that both BMP7 and Pax6 play important roles during embryonic SMG branching morphogenesis. ..
  2. Mailleux A, Spencer Dene B, Dillon C, Ndiaye D, Savona Baron C, Itoh N, et al. Role of FGF10/FGFR2b signaling during mammary gland development in the mouse embryo. Development. 2002;129:53-60 pubmed
    ..Our results also suggest that FGF signaling is involved in the maintenance of mammary bud 4, and that Fgf10 deficient epithelium can undergo branching morphogenesis into the mammary fat pad precursor. ..
  3. Pérez Romero A, Dialynas E, Salame F, Amores A, Vidarte L, Bartke A, et al. GH gene expression in the submaxillary gland in normal and Ames dwarf mice. J Endocrinol. 2001;169:389-96 pubmed
    ..The present experiment demonstrates that salivary tissue synthesizes GH when it is exposed to the influence of GHRH. Both basal and GHRH-induced salivary GH expression appear to be independent of Pit-1. ..
  4. Rubert G, Miñana R, Pascual M, Guerri C. Ethanol exposure during embryogenesis decreases the radial glial progenitorpool and affects the generation of neurons and astrocytes. J Neurosci Res. 2006;84:483-96 pubmed
    ..Moreover, levels of activated Notch1 and fibroblast growth factor receptor 2, which regulate the maintenance of the progenitor state of RG, are decreased by prenatal ethanol ..
  5. Steele I, Edmondson R, Bulmer J, Bolger B, Leung H, Davies B. Induction of FGF receptor 2-IIIb expression and response to its ligands in epithelial ovarian cancer. Oncogene. 2001;20:5878-87 pubmed
    ..b>Fibroblast Growth Factor Receptor 2 isoform IIIb (FGF receptor 2-IIIb) is a spliced variant of FGF receptor 2 that binds the ligands ..
  6. Patel V, Knox S, Likar K, Lathrop C, Hossain R, Eftekhari S, et al. Heparanase cleavage of perlecan heparan sulfate modulates FGF10 activity during ex vivo submandibular gland branching morphogenesis. Development. 2007;134:4177-86 pubmed
    ..In summary, our results show heparanase releases FGF10 from perlecan HS in the basement membrane, increasing MAPK signaling, epithelial clefting, and lateral branch formation, which results in increased branching morphogenesis. ..
  7. Passos Bueno M, Sertié A, Richieri Costa A, Alonso L, Zatz M, Alonso N, et al. Description of a new mutation and characterization of FGFR1, FGFR2, and FGFR3 mutations among Brazilian patients with syndromic craniosynostoses. Am J Med Genet. 1998;78:237-41 pubmed
    ..In addition, we identified a new mutation (A337P) in the FGFR2 exon IIIc associated with Crouzon phenotype. ..
  8. Hattori Y, Itoh H, Uchino S, Hosokawa K, Ochiai A, Ino Y, et al. Immunohistochemical detection of K-sam protein in stomach cancer. Clin Cancer Res. 1996;2:1373-81 pubmed
    ..These results suggest that K-sam overexpression is associated with the malignant phenotype of the undifferentiated type of stomach cancer, such as infiltrative growth and metastasis. ..
  9. Miyake A, Hattori Y, Ohta M, Itoh N. Rat oligodendrocytes and astrocytes preferentially express fibroblast growth factor receptor-2 and -3 mRNAs. J Neurosci Res. 1996;45:534-41 pubmed
    ..The expression of FGFR-2 IIIc and FGFR-3 IIIc with different ligand specificities might play important roles in the various effects of FGFs on oligodendrocytes and astrocytes. ..

More Information


  1. Lonic A, Powell J, Kong Y, Thomas D, Holien J, Truong N, et al. Phosphorylation of serine 779 in fibroblast growth factor receptor 1 and 2 by protein kinase C(epsilon) regulates Ras/mitogen-activated protein kinase signaling and neuronal differentiation. J Biol Chem. 2013;288:14874-85 pubmed publisher
    ..Our findings show that in addition to FGFR tyrosine phosphorylation, the phosphorylation of a conserved serine residue, Ser(779), can quantitatively control Ras/MAPK signaling to promote specific cellular responses. ..
  2. Plotnikov A, Hubbard S, Schlessinger J, Mohammadi M. Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity. Cell. 2000;101:413-24 pubmed
    ..These structures provide a molecular basis for FGF1 as a universal FGFR ligand and for modulation of FGF-FGFR specificity through primary sequence variations and alternative splicing. ..
  3. Zhao Z, Pollock P, Thomas S, Treloar S, Nyholt D, Montgomery G. Common variation in the fibroblast growth factor receptor 2 gene is not associated with endometriosis risk. Hum Reprod. 2008;23:1661-8 pubmed publisher
    ..Epidemiological data support a link between endometriosis and cancers of the reproductive tract. Fibroblast growth factor receptor 2 (FGFR2) has recently been implicated in both endometrial and breast cancer...
  4. Rouzier C, Soler C, Hofman P, Brennetot C, Bieth E, Pedeutour F. Ovarian dysgerminoma and Apert syndrome. Pediatr Blood Cancer. 2008;50:696-8 pubmed
    ..This is the second report of the association of Apert syndrome with cancer. Our observation raises the hypothesis of a role for FGFR2 mutations in tumorigenesis. ..
  5. White K, Cabral J, Davis S, Fishburn T, Evans W, Ichikawa S, et al. Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation. Am J Hum Genet. 2005;76:361-7 pubmed
  6. Cha J, Maddileti S, Mitin N, Harden T, Der C. Aberrant receptor internalization and enhanced FRS2-dependent signaling contribute to the transforming activity of the fibroblast growth factor receptor 2 IIIb C3 isoform. J Biol Chem. 2009;284:6227-40 pubmed publisher
    Alternative splice variants of fibroblast growth factor receptor 2 (FGFR2) IIIb, designated C1, C2, and C3, possess progressive reduction in their cytoplasmic carboxyl termini (822, 788, and 769 residues, respectively), with preferential ..
  7. McGrath M, Lee I, Buring J, Hunter D, De Vivo I. Novel breast cancer risk alleles and endometrial cancer risk. Int J Cancer. 2008;123:2961-4 pubmed publisher
    ..The molecular mechanisms underlying these differences remain to be defined. ..
  8. Zhao H, Yang T, Madakashira B, Thiels C, Bechtle C, Garcia C, et al. Fibroblast growth factor receptor signaling is essential for lens fiber cell differentiation. Dev Biol. 2008;318:276-88 pubmed publisher
    ..Therefore, while signaling by FGF receptors is essential for lens fiber differentiation, different FGF receptors function redundantly. ..
  9. Naimi B, Latil A, Fournier G, Mangin P, Cussenot O, Berthon P. Down-regulation of (IIIb) and (IIIc) isoforms of fibroblast growth factor receptor 2 (FGFR2) is associated with malignant progression in human prostate. Prostate. 2002;52:245-52 pubmed
  10. Wagner E, Baraniak A, Sessions O, Mauger D, Moskowitz E, Garcia Blanco M. Characterization of the intronic splicing silencers flanking FGFR2 exon IIIb. J Biol Chem. 2005;280:14017-27 pubmed
    ..Our data defined elements of function within the ISSs flanking exon IIIb and suggested that silencing of this exon is mediated by multiple trans-acting factors. ..
  11. Fonseca R, Costa Lima M, Cosentino V, Orioli I. Second case of Beare-Stevenson syndrome with an FGFR2 Ser372Cys mutation. Am J Med Genet A. 2008;146A:658-60 pubmed publisher
    ..Reported causes are an FGFR2 Tyr375Cys mutation in nine cases and an FGFR2 Ser372Cys mutation in one case. Here, we report on a second patient with the FGFR2 Ser372Cys mutation. ..
  12. Spencer Dene B, Sala F, Bellusci S, Gschmeissner S, Stamp G, Dickson C. Stomach development is dependent on fibroblast growth factor 10/fibroblast growth factor receptor 2b-mediated signaling. Gastroenterology. 2006;130:1233-44 pubmed
    ..Fgfr2b and Fgf10 are part of a signaling network with Sonic hedgehog and Indian hedgehog that are essential to anterior-posterior and radial patterning in gastric development. ..
  13. Easton D, Pooley K, Dunning A, Pharoah P, Thompson D, Ballinger D, et al. Genome-wide association study identifies novel breast cancer susceptibility loci. Nature. 2007;447:1087-93 pubmed
    ..05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach. ..
  14. Tsai F, Yang C, Wu J, Tsai C, Lee C. Mutation analysis of Crouzon syndrome and identification of one novel mutation in Taiwanese patients. Pediatr Int. 2001;43:263-6 pubmed
    ..Mutations have been reported in exon IIIa or IIIc of the fibroblast growth factor receptor 2 (FGFR2) gene...
  15. Mehta P, Robson C, Neal D, Leung H. Fibroblast growth factor receptor-2 mutation analysis in human prostate cancer. BJU Int. 2000;86:681-5 pubmed
    ..FGFR2 mutations in the-FGF binding domain and the TMD are not frequent events in human prostate cancer. ..
  16. von Gernet S, Golla A, Ehrenfels Y, Schuffenhauer S, Fairley J. Genotype-phenotype analysis in Apert syndrome suggests opposite effects of the two recurrent mutations on syndactyly and outcome of craniofacial surgery. Clin Genet. 2000;57:137-9 pubmed
    ..characterized by craniosynostosis and severe syndactyly, caused by two recurrent mutations in the fibroblast growth factor receptor 2 gene (FGFR2)...
  17. Carstens R, McKeehan W, Garcia Blanco M. An intronic sequence element mediates both activation and repression of rat fibroblast growth factor receptor 2 pre-mRNA splicing. Mol Cell Biol. 1998;18:2205-17 pubmed
    Alternative splicing of fibroblast growth factor receptor 2 (FGF-R2) is an example of highly regulated alternative splicing in which exons IIIb and IIIc are utilized in a mutually exclusive manner in different cell types...
  18. Jiang J, Xu H, Zhu Y, Wood K, Li E, Sun W, et al. Reduced Fgf10/Fgfr2 and androgen receptor (AR) in anorectal malformations male rats induced by di-n-butyl phthalate (DBP): A study on the local and systemic toxicology of DBP. Toxicology. 2015;338:77-85 pubmed publisher
    ..Our findings suggest the potential involvement of altered Fgf10/Fgfr2 signaling and AR in pathogenesis of local and systemic development defects in ARMs male rats induce by DBP. ..
  19. Lazarus J, Hegde A, Andrade A, Nilsson O, Baron J. Fibroblast growth factor expression in the postnatal growth plate. Bone. 2007;40:577-86 pubmed
    ..We also found temporal changes in FGF and FGFR expression which may contribute to growth plate senescence and thus help determine the size of the adult skeleton. ..
  20. Schuller A, Ahmed Z, Ladbury J. Extracellular point mutations in FGFR2 result in elevated ERK1/2 activation and perturbation of neuronal differentiation. Biochem J. 2008;410:205-11 pubmed
    ..gain-of-function point mutations (S252W and P253R) in the extracellular region of the FGFR2 (fibroblast growth factor receptor 2) increase the binding affinity for the growth factor...
  21. Muratore C, Luks F, Zhou Y, Harty M, Reichner J, Tracy T. Endotoxin alters early fetal lung morphogenesis. J Surg Res. 2009;155:225-30 pubmed publisher
  22. Yu J, Jeong S, Yang J, Park M, Kim H, Yoon S. Genotypic and phenotypic analyses of Korean patients with syndromic craniosynostosis. Clin Genet. 2009;76:287-91 pubmed publisher
  23. Shen K, Krakora S, Cunningham M, Singh M, Wang X, Hu F, et al. Medical treatment of craniosynostosis: recombinant Noggin inhibits coronal suture closure in the rat craniosynostosis model. Orthod Craniofac Res. 2009;12:254-62 pubmed publisher
    ..Topical application of rhNoggin protein prevents craniosynostosis in the weanling nude rat xenotransplantation model of syndromic craniosynostosis...
  24. Shigematsu A, Shi M, Okigaki M, Adachi Y, Koike N, Che J, et al. Signaling from fibroblast growth factor receptor 2 in immature hematopoietic cells facilitates donor hematopoiesis after intra-bone marrow-bone marrow transplantation. Stem Cells Dev. 2010;19:1679-86 pubmed publisher
    ..These results suggest that the antiapoptotic effect of FGFR2 signaling facilitates the hematopoiesis of FGFR2 Tg mice. ..
  25. Stevens H, Smith K, Maragnoli M, Fagel D, Borok E, Shanabrough M, et al. Fgfr2 is required for the development of the medial prefrontal cortex and its connections with limbic circuits. J Neurosci. 2010;30:5590-602 pubmed publisher
    ..These data demonstrate that FGFR2 signaling expands the number of excitatory neurons in the mPFC and secondarily influences target neurons in subcortical stations of the limbic system. ..
  26. Barge Schaapveld D, Brooks A, Lequin M, van Spaendonk R, Vermeulen R, Cobben J. Beare-Stevenson syndrome: two Dutch patients with cerebral abnormalities. Pediatr Neurol. 2011;44:303-7 pubmed publisher
    ..In 1996, two mutations in the fibroblast growth factor receptor 2 gene were found to cause this syndrome, thereby including BSS in the fibroblast growth factor ..
  27. Arman E, Haffner Krausz R, Gorivodsky M, Lonai P. Fgfr2 is required for limb outgrowth and lung-branching morphogenesis. Proc Natl Acad Sci U S A. 1999;96:11895-9 pubmed
    ..Possible epithelial-mesenchymal interactions between the splicing alternatives of Fgfr2 and their specific ligands will be discussed. ..
  28. Hatch N, Hudson M, Seto M, Cunningham M, Bothwell M. Intracellular retention, degradation, and signaling of glycosylation-deficient FGFR2 and craniosynostosis syndrome-associated FGFR2C278F. J Biol Chem. 2006;281:27292-305 pubmed
  29. Schmahl J, Kim Y, Colvin J, Ornitz D, Capel B. Fgf9 induces proliferation and nuclear localization of FGFR2 in Sertoli precursors during male sex determination. Development. 2004;131:3627-36 pubmed
    ..The nuclear localization of FGFR2 coincides with the initiation of Sry expression and the nuclear localization of SOX9 during the early differentiation of Sertoli cells and the determination of male fate. ..
  30. Petiot A, Perriton C, Dickson C, Cohn M. Development of the mammalian urethra is controlled by Fgfr2-IIIb. Development. 2005;132:2441-50 pubmed
    ..We report that mice lacking the IIIb isoform of fibroblast growth factor receptor 2 (Fgfr2) exhibit severe hypospadias...
  31. Yoon K, Nery S, Rutlin M, Radtke F, Fishell G, Gaiano N. Fibroblast growth factor receptor signaling promotes radial glial identity and interacts with Notch1 signaling in telencephalic progenitors. J Neurosci. 2004;24:9497-506 pubmed
  32. Wang J, Cai X, Zou M, Xu T, Liu S, Wang Y, et al. Construction and characterization of a high activity mutant of human keratinocyte growth factor-2. Biotechnol Lett. 2009;31:797-802 pubmed publisher
    ..These results suggest that the simultaneous mutation of Ser115 to Thr and Glu117 to Ala improves the biological activity of KGF-2. ..
  33. Yin Y, White A, Huh S, Hilton M, Kanazawa H, Long F, et al. An FGF-WNT gene regulatory network controls lung mesenchyme development. Dev Biol. 2008;319:426-36 pubmed publisher
    ..Together, both FGF and WNT signaling pathways function to sustain mesenchymal growth and coordinate epithelial morphogenesis during the pseudoglandular stage of lung development. ..
  34. Tsuchioka M, Takebayashi M, Hisaoka K, Maeda N, Nakata Y. Serotonin (5-HT) induces glial cell line-derived neurotrophic factor (GDNF) mRNA expression via the transactivation of fibroblast growth factor receptor 2 (FGFR2) in rat C6 glioma cells. J Neurochem. 2008;106:244-57 pubmed publisher
    ..In conclusion, our findings suggest that 5-HT induces GDNF mRNA expression via 5-HT(2)R-mediated FGFR2 transactivation in C6 cells. ..
  35. Manavi M, Hudelist G, Fink Retter A, Gschwandtler Kaulich D, Pischinger K, Czerwenka K. Gene profiling in Pap-cell smears of high-risk human papillomavirus-positive squamous cervical carcinoma. Gynecol Oncol. 2007;105:418-26 pubmed
    ..We observed gene expression patterns and signaling pathways that permit the investigator to distinguish between benign squamous cervical cells and CSCC with and without HPV infection. ..
  36. Oltean S, Sorg B, Albrecht T, Bonano V, Brazas R, Dewhirst M, et al. Alternative inclusion of fibroblast growth factor receptor 2 exon IIIc in Dunning prostate tumors reveals unexpected epithelial mesenchymal plasticity. Proc Natl Acad Sci U S A. 2006;103:14116-21 pubmed
    In epithelial cells, alternative splicing of fibroblast growth factor receptor 2 (FGFR2) transcripts leads to the expression of the FGFR2(IIIb) isoform, whereas in mesenchymal cells, the same process results in the synthesis of FGFR2(..
  37. Marguerie A, Bajolle F, Zaffran S, Brown N, Dickson C, Buckingham M, et al. Congenital heart defects in Fgfr2-IIIb and Fgf10 mutant mice. Cardiovasc Res. 2006;71:50-60 pubmed
    ..Fgfr2-IIIb and Fgf10 mutant mice provide new models for common components of congenital heart disease. ..
  38. Fairbanks T, Kanard R, Del Moral P, Sala F, De Langhe S, Warburton D, et al. Fibroblast growth factor receptor 2 IIIb invalidation--a potential cause of familial duodenal atresia. J Pediatr Surg. 2004;39:872-4 pubmed
    ..Fgfr2b invalidation (Fgfr2b-/- mutant) results in a reproducible, autosomal recessive duodenal atresia phenotype with incomplete penetrance and a variable phenotype. ..
  39. Ceridono M, Belleudi F, Ceccarelli S, Torrisi M. Tyrosine 769 of the keratinocyte growth factor receptor is required for receptor signaling but not endocytosis. Biochem Biophys Res Commun. 2005;327:523-32 pubmed
    ..Our data also show that tyrosine 769 is not involved in the regulation of the endocytic process of KGFR. ..
  40. Reardon W, Smith A, Honour J, Hindmarsh P, Das D, Rumsby G, et al. Evidence for digenic inheritance in some cases of Antley-Bixler syndrome?. J Med Genet. 2000;37:26-32 pubmed
  41. Madakashira B, Kobrinski D, Hancher A, Arneman E, Wagner B, Wang F, et al. Frs2? enhances fibroblast growth factor-mediated survival and differentiation in lens development. Development. 2012;139:4601-12 pubmed publisher
    ..Therefore, tyrosine phosphorylation of Frs2? mediates Fgfr-dependent lens cell survival and provides a mechanistic basis for the unique fiber-differentiating capacity of Fgfs on mammalian lens epithelial cells. ..
  42. Merrill A, Sarukhanov A, Krejci P, Idoni B, Camacho N, Estrada K, et al. Bent bone dysplasia-FGFR2 type, a distinct skeletal disorder, has deficient canonical FGF signaling. Am J Hum Genet. 2012;90:550-7 pubmed publisher
    b>Fibroblast growth factor receptor 2 (FGFR2) is a crucial regulator of bone formation during embryonic development...
  43. Onda M, Naito Z, Wang R, Fujii T, Kawahara K, Ishiwata T, et al. Expression of keratinocyte growth factor receptor (KGFR/FGFR2 IIIb) in vascular smooth muscle cells. Pathol Int. 2003;53:127-32 pubmed
    ..Recombinant FGF-7 and/or FGF-10 proteins stimulated the growth of cultured rat VSMC. These findings indicate that KGFR localized in VSMC may contribute to the proliferation of VSMC in normal and atherosclerotic arteries. ..
  44. Marker P, Dahiya R, Cunha G. Spontaneous mutation in mice provides new insight into the genetic mechanisms that pattern the seminal vesicles and prostate gland. Dev Dyn. 2003;226:643-53 pubmed
  45. Albrecht P, Murtie J, Ness J, Redwine J, Enterline J, Armstrong R, et al. Astrocytes produce CNTF during the remyelination phase of viral-induced spinal cord demyelination to stimulate FGF-2 production. Neurobiol Dis. 2003;13:89-101 pubmed
    ..Altogether, these results strongly implicate CNTF as an important cytokine in demyelinating disease and as an upstream regulator of FGF-2 production in astrocytes during early remyelination. ..
  46. Pollock P, Gartside M, Dejeza L, Powell M, Mallon M, Davies H, et al. Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes. Oncogene. 2007;26:7158-62 pubmed
    ..The discovery of activating FGFR2 mutations in endometrial carcinoma raises the possibility of employing anti-FGFR molecularly targeted therapies in patients with advanced or recurrent endometrial carcinoma. ..
  47. Andreou A, Lamy A, Layet V, Cailliez D, Gobet F, Pfister C, et al. Early-onset low-grade papillary carcinoma of the bladder associated with Apert syndrome and a germline FGFR2 mutation (Pro253Arg). Am J Med Genet A. 2006;140:2245-7 pubmed
  48. Veltmaat J, Relaix F, Le L, Kratochwil K, Sala F, Van Veelen W, et al. Gli3-mediated somitic Fgf10 expression gradients are required for the induction and patterning of mammary epithelium along the embryonic axes. Development. 2006;133:2325-35 pubmed
    ..We propose that the intra-somitic Fgf10 gradient, together with ventral elongation of the somites, determines the correct dorsoventral position of mammary epithelium along the flank. ..
  49. Hovhannisyan R, Carstens R. A novel intronic cis element, ISE/ISS-3, regulates rat fibroblast growth factor receptor 2 splicing through activation of an upstream exon and repression of a downstream exon containing a noncanonical branch point sequence. Mol Cell Biol. 2005;25:250-63 pubmed
    Mutually exclusive splicing of fibroblast growth factor receptor 2 (FGFR2) exons IIIb and IIIc yields two receptor isoforms, FGFR2-IIIb and -IIIc, with distinctly different ligand binding properties...
  50. Spilde T, Bhatia A, Mehta S, Hembree M, Preuett B, Ostlie D, et al. Aberrant fibroblast growth factor receptor 2 signalling in esophageal atresia with tracheoesophageal fistula. J Pediatr Surg. 2004;39:537-9 pubmed
    ..This defect in FGF2RIIIb signaling may account for the nonbranching, esophaguslike phenotype of the fistula, despite its respiratory origin. ..
  51. Jaskoll T, Abichaker G, Witcher D, Sala F, Bellusci S, Hajihosseini M, et al. FGF10/FGFR2b signaling plays essential roles during in vivo embryonic submandibular salivary gland morphogenesis. BMC Dev Biol. 2005;5:11 pubmed
  52. Luo Y, Yang C, Jin C, Xie R, Wang F, McKeehan W. Novel phosphotyrosine targets of FGFR2IIIb signaling. Cell Signal. 2009;21:1370-8 pubmed publisher
    ..Our findings provide specific downstream targets for dissection of causal relationships underlying the distinct role of FGF7/FGFR2IIIb signaling in epithelial cell homeostasis. ..
  53. Billottet C, Elkhatib N, Thiery J, Jouanneau J. Targets of fibroblast growth factor 1 (FGF-1) and FGF-2 signaling involved in the invasive and tumorigenic behavior of carcinoma cells. Mol Biol Cell. 2004;15:4725-34 pubmed
    ..These molecular analyses show that the potential of these two growth factors in tumor progression is highly dependent on specific FGFR signaling and highlights its importance as a target for antitumor therapy. ..