Gene Symbol: Fgfr4
Description: fibroblast growth factor receptor 4
Alias: Fgfr-4, fibroblast growth factor receptor 4, CTLA-2-beta protein, fibroblast growth factor receptor 4 16 minus form, protein-tyrosine kinase receptor MPK-11
Species: mouse
Products:     Fgfr4

Top Publications

  1. Kurosu H, Choi M, Ogawa Y, Dickson A, Goetz R, Eliseenkova A, et al. Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. J Biol Chem. 2007;282:26687-95 pubmed
    ..Additionally, both FGF19 and FGF21 bind to the betaKlotho-FGFR4 complex; however, only FGF19 signals efficiently through FGFR4...
  2. Kurosu H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, Rosenblatt K, et al. Regulation of fibroblast growth factor-23 signaling by klotho. J Biol Chem. 2006;281:6120-3 pubmed
    ..Thus, Klotho functions as a cofactor essential for activation of FGF signaling by FGF23. ..
  3. Huang X, Yang C, Luo Y, Jin C, Wang F, McKeehan W. FGFR4 prevents hyperlipidemia and insulin resistance but underlies high-fat diet induced fatty liver. Diabetes. 2007;56:2501-10 pubmed
    ..The objective was to determine the role of FGFR4, an isotype that has been proposed to mediate an ileal FGF15/19 to hepatocyte FGFR4 axis in cholesterol ..
  4. Inagaki T, Choi M, Moschetta A, Peng L, Cummins C, McDonald J, et al. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab. 2005;2:217-25 pubmed
    ..the nuclear bile acid receptor FXR and represses Cyp7a1 in liver through a mechanism that involves FGF receptor 4 (FGFR4) and the orphan nuclear receptor SHP...
  5. Ogawa Y, Kurosu H, Yamamoto M, Nandi A, Rosenblatt K, Goetz R, et al. BetaKlotho is required for metabolic activity of fibroblast growth factor 21. Proc Natl Acad Sci U S A. 2007;104:7432-7 pubmed
    ..Importantly, administration of FGF21 into mice induces MAP kinase phosphorylation in white adipose tissue and not in tissues without betaKlotho expression. Thus, betaKlotho functions as a cofactor essential for FGF21 activity. ..
  6. Weinstein M, Xu X, Ohyama K, Deng C. FGFR-3 and FGFR-4 function cooperatively to direct alveogenesis in the murine lung. Development. 1998;125:3615-23 pubmed
    ..These data revealed a cooperative function of FGFR-3 and FGFR-4 to promote the formation of alveoli during postnatal lung development. ..
  7. Coumoul X, Shukla V, Li C, Wang R, Deng C. Conditional knockdown of Fgfr2 in mice using Cre-LoxP induced RNA interference. Nucleic Acids Res. 2005;33:e102 pubmed
    ..This method provides a fast, yet efficient way to decipher gene functions in vivo in a tissue-specific manner. ..
  8. Wu X, Ge H, Lemon B, Vonderfecht S, Weiszmann J, Hecht R, et al. FGF19-induced hepatocyte proliferation is mediated through FGFR4 activation. J Biol Chem. 2010;285:5165-70 pubmed publisher
    ..We find that although both are able to activate FGF receptors (FGFRs) 1c, 2c, and 3c, only FGF19 activates FGFR4, the predominant receptor in the liver...
  9. Grieshammer U, Cebrian C, Ilagan R, Meyers E, Herzlinger D, Martin G. FGF8 is required for cell survival at distinct stages of nephrogenesis and for regulation of gene expression in nascent nephrons. Development. 2005;132:3847-57 pubmed
    ..Thus, unlike other FGF family members, which regulate growth and branching morphogenesis of the collecting duct system, Fgf8 encodes a factor essential for gene regulation and cell survival at distinct steps in nephrogenesis. ..

More Information


  1. Yu C, Wang F, Kan M, Jin C, Jones R, Weinstein M, et al. Elevated cholesterol metabolism and bile acid synthesis in mice lacking membrane tyrosine kinase receptor FGFR4. J Biol Chem. 2000;275:15482-9 pubmed
    Heparan sulfate-regulated transmembrane tyrosine kinase receptor FGFR4 is the major FGFR isotype in mature hepatocytes...
  2. Suzuki M, Uehara Y, Motomura Matsuzaka K, Oki J, Koyama Y, Kimura M, et al. betaKlotho is required for fibroblast growth factor (FGF) 21 signaling through FGF receptor (FGFR) 1c and FGFR3c. Mol Endocrinol. 2008;22:1006-14 pubmed publisher
    ..It is thus suggested that betaKlotho expression is a crucial determinant of the FGF21 specificity of the target cells upon which it acts in an endocrine fashion. ..
  3. Huang X, Yang C, Jin C, Luo Y, Wang F, McKeehan W. Resident hepatocyte fibroblast growth factor receptor 4 limits hepatocarcinogenesis. Mol Carcinog. 2009;48:553-62 pubmed publisher
    ..Of the FGF receptor (FGFR) isotypes, FGFR4 is the sole resident isotype present in mature parenchymal hepatocytes...
  4. Lin Y, Chen L, Lin C, Luo Y, Tsai R, Wang F. Neuron-derived FGF9 is essential for scaffold formation of Bergmann radial fibers and migration of granule neurons in the cerebellum. Dev Biol. 2009;329:44-54 pubmed publisher
    ..This work demonstrates that granule neurons secrete FGF9 to control formation of the Bergmann fiber scaffold, which in turn, guides their own inward migration and maturation of Purkinje cells. ..
  5. Wiedemann M, Trueb B. The mouse Fgfrl1 gene coding for a novel FGF receptor-like protein. Biochim Biophys Acta. 2001;1520:247-50 pubmed
    ..The gene for Fgfrl1 comprises six exons and is located on mouse chromosome 5 in close proximity to the Idua gene for L-iduronidase. ..
  6. Seitzer N, Mayr T, Streit S, Ullrich A. A single nucleotide change in the mouse genome accelerates breast cancer progression. Cancer Res. 2010;70:802-12 pubmed publisher
    In the growth factor receptor gene FGFR4 the presence of the common single nucleotide polymorphism Arg388 has been associated with progression of various types of cancer including breast cancer...
  7. Wu X, Ge H, Lemon B, Weiszmann J, Gupte J, Hawkins N, et al. Selective activation of FGFR4 by an FGF19 variant does not improve glucose metabolism in ob/ob mice. Proc Natl Acad Sci U S A. 2009;106:14379-84 pubmed publisher
    ..was essential for FGF19 interaction with FGFRs 1c, 2c, and 3c, but FGF19 was able to interact directly with FGFR4 in the absence of betaKlotho in a heparin-dependent manner...
  8. Blak A, Naserke T, Weisenhorn D, Prakash N, Partanen J, Wurst W. Expression of Fgf receptors 1, 2, and 3 in the developing mid- and hindbrain of the mouse. Dev Dyn. 2005;233:1023-30 pubmed
    ..Fgfr3 expression is in contact with the Fgf8 expression domain only in the rostroventral hindbrain. Based on these findings, we postulate a role for FGFR2 and FGFR3 in FGF signaling in the ventral midbrain and hindbrain. ..
  9. Luo Y, Yang C, Lu W, Xie R, Jin C, Huang P, et al. Metabolic regulator betaKlotho interacts with fibroblast growth factor receptor 4 (FGFR4) to induce apoptosis and inhibit tumor cell proliferation. J Biol Chem. 2010;285:30069-78 pubmed publisher
    ..Coordinate expression of ?klotho and FGFR4 is a property of mature hepatocytes...
  10. Sylvestersen K, Herrera P, Serup P, Rescan C. Fgf9 signalling stimulates Spred and Sprouty expression in embryonic mouse pancreas mesenchyme. Gene Expr Patterns. 2011;11:105-11 pubmed publisher
  11. Thomas T, Voss A, Petrou P, Gruss P. The murine gene, Traube, is essential for the growth of preimplantation embryos. Dev Biol. 2000;227:324-42 pubmed
    ..This paucity of ribosomes together with the localization of TRB to the nucleoli, the site of ribosome synthesis, suggests that TRB is involved in the synthesis of ribosomes. ..
  12. Becker M, Bräuninger A, Wolf G, Kaufmann M, Strebhardt K. Identification and functional characterization of the human and murine fibroblast growth factor receptor 4 promoters. Biochem Biophys Res Commun. 2000;276:493-501 pubmed
    ..To study the transcriptional control, we isolated and characterized the promoter of human FGFR4. Two transcription initiation sites were identified...
  13. Hurlin P, Queva C, Koskinen P, Steingrimsson E, Ayer D, Copeland N, et al. Mad3 and Mad4: novel Max-interacting transcriptional repressors that suppress c-myc dependent transformation and are expressed during neural and epidermal differentiation. EMBO J. 1995;14:5646-59 pubmed
  14. Gattineni J, Twombley K, Goetz R, Mohammadi M, Baum M. Regulation of serum 1,25(OH)2 vitamin D3 levels by fibroblast growth factor 23 is mediated by FGF receptors 3 and 4. Am J Physiol Renal Physiol. 2011;301:F371-7 pubmed publisher
    ..To determine the FGFRs regulating 1,25(OH)(2)Vitamin D(3) levels, we studied FGFR3(-/-)FGFR4(-/-) mice as these mice have shortened life span and are growth retarded similar to FGF23(-/-) and Klotho(-/-) ..
  15. Kitagaki J, Ueda Y, Chi X, Sharma N, Elder C, Truffer E, et al. FGF8 is essential for formation of the ductal system in the male reproductive tract. Development. 2011;138:5369-78 pubmed publisher
    ..These results demonstrate a multifocal requirement for FGF8 in establishing the male reproductive tract ducts and implicate Lhx1 signaling in tubule elongation. ..
  16. Chan K, Wong H, Jin G, Liu B, Cao R, Cao Y, et al. MT1-MMP inactivates ADAM9 to regulate FGFR2 signaling and calvarial osteogenesis. Dev Cell. 2012;22:1176-90 pubmed publisher
    ..These data reveal a regulatory paradigm for FGRF2 signaling and identify MT1-MMP as a critical negative modulator of ADAM9 activity to maintain FGFR2 signaling in calvarial osteogenesis. ..
  17. Green M, Myat A, Emmenegger B, Wechsler Reya R, Wilson L, Wingate R. Independently specified Atoh1 domains define novel developmental compartments in rhombomere 1. Development. 2014;141:389-98 pubmed publisher
    ..This suggests that although the isthmus regulates the size of the cerebellar anlage, the downregulation of isthmic FGF signals is required for induction of rhombic lip-derived cerebellar neurons. ..
  18. Gilardi Hebenstreit P, Nieto M, Frain M, Mattei M, Chestier A, Wilkinson D, et al. An Eph-related receptor protein tyrosine kinase gene segmentally expressed in the developing mouse hindbrain. Oncogene. 1992;7:2499-506 pubmed
    ..These data are consistent with a role of the Sek gene product in a signal transduction process involved in pattern formation in the hindbrain. ..
  19. Bagheri Fam S, Bird A, Zhao L, Ryan J, Yong M, Wilhelm D, et al. Testis Determination Requires a Specific FGFR2 Isoform to Repress FOXL2. Endocrinology. 2017;158:3832-3843 pubmed publisher
    ..Together with previous findings, our data suggest that testis determination involves FGFR2c-mediated repression of both the WNT4- and FOXL2-driven ovarian-determining pathways. ..
  20. Bachler M, Neubüser A. Expression of members of the Fgf family and their receptors during midfacial development. Mech Dev. 2001;100:313-6 pubmed
    ..5. In contrast to the restricted expression patterns of the ligands, FgfR1 and FgfR2 were broadly expressed in facial mesenchyme and ectoderm, respectively, indicating a wide competence of midfacial tissue to respond to FGF signaling. ..
  21. Zhao P, Caretti G, Mitchell S, McKeehan W, Boskey A, Pachman L, et al. Fgfr4 is required for effective muscle regeneration in vivo. Delineation of a MyoD-Tead2-Fgfr4 transcriptional pathway. J Biol Chem. 2006;281:429-38 pubmed
    b>Fgfr4 has been shown to be important for appropriate muscle development in chick limb buds; however, Fgfr4 null mice show no phenotype...
  22. Hoffman M, Kidder B, Steinberg Z, Lakhani S, Ho S, Kleinman H, et al. Gene expression profiles of mouse submandibular gland development: FGFR1 regulates branching morphogenesis in vitro through BMP- and FGF-dependent mechanisms. Development. 2002;129:5767-78 pubmed
    ..Taken together, our results suggest specific FGFs and BMPs play reciprocal roles in regulating branching morphogenesis and FGFR1 signaling plays a central role by regulating both FGF and BMP expression. ..
  23. Cardoso W, Itoh A, Nogawa H, Mason I, Brody J. FGF-1 and FGF-7 induce distinct patterns of growth and differentiation in embryonic lung epithelium. Dev Dyn. 1997;208:398-405 pubmed
    ..Thus, in the embryonic lung epithelium, growth effects of FGFs appear to be dependent on location of FGFRs, while effects on differentiation are ligand-dependent. ..
  24. Li J, Miao L, Zhao C, Shaikh Qureshi W, Shieh D, Guo H, et al. CDC42 is required for epicardial and pro-epicardial development by mediating FGF receptor trafficking to the plasma membrane. Development. 2017;144:1635-1647 pubmed publisher
    ..FGF signaling promotes epicardium formation in vivo, and biochemical studies demonstrated that CDC42 is involved in the trafficking of FGF receptors to the cell membrane to regulate epicardium formation. ..
  25. Beirowski B, Morreale G, Conforti L, Mazzola F, Di Stefano M, Wilbrey A, et al. WldS can delay Wallerian degeneration in mice when interaction with valosin-containing protein is weakened. Neuroscience. 2010;166:201-11 pubmed publisher
    ..We suggest that either N16 has an additional, VCP-independent function in mammals, or that the phenotype requires only weak VCP binding which may be driven forwards in vivo by the high VCP concentration...
  26. Han D, Zhao H, Parada C, Hacia J, Bringas P, Chai Y. A TGF?-Smad4-Fgf6 signaling cascade controls myogenic differentiation and myoblast fusion during tongue development. Development. 2012;139:1640-50 pubmed publisher
    ..of Smad4 results in a significant reduction in expression of several members of the FGF family, including Fgf6 and Fgfr4. Exogenous Fgf6 partially rescues the tongue myoblast fusion defect of Myf5-Cre;Smad4(flox/flox) mice...
  27. Yablonka Reuveni Z, Danoviz M, Phelps M, Stuelsatz P. Myogenic-specific ablation of Fgfr1 impairs FGF2-mediated proliferation of satellite cells at the myofiber niche but does not abolish the capacity for muscle regeneration. Front Aging Neurosci. 2015;7:85 pubmed publisher
    ..Using the mouse model, we show here that of the four Fgfr genes, only Fgfr1 and Fgfr4 are expressed at relatively high levels in quiescent SCs and their proliferating progeny...
  28. French D, Lin B, Wang M, Adams C, Shek T, Hotzel K, et al. Targeting FGFR4 inhibits hepatocellular carcinoma in preclinical mouse models. PLoS ONE. 2012;7:e36713 pubmed publisher
    ..The FGFR4-FGF19 signaling axis has been implicated in the development of hepatocellular carcinomas (HCCs) in mice, and ..
  29. Iwabuchi T, Goetinck P. Syndecan-4 dependent FGF stimulation of mouse vibrissae growth. Mech Dev. 2006;123:831-41 pubmed
  30. Seymour P, Shih H, Patel N, Freude K, Xie R, Lim C, et al. A Sox9/Fgf feed-forward loop maintains pancreatic organ identity. Development. 2012;139:3363-72 pubmed publisher
    ..This self-promoting Sox9/Fgf10/Fgfr2b loop may regulate cell identity and organ size in a broad spectrum of developmental and regenerative contexts. ..
  31. Lagha M, Kormish J, Rocancourt D, Manceau M, Epstein J, Zaret K, et al. Pax3 regulation of FGF signaling affects the progression of embryonic progenitor cells into the myogenic program. Genes Dev. 2008;22:1828-37 pubmed publisher
    Pax3/7-dependent stem cells play an essential role in skeletal muscle development. We now show that Fgfr4 lies genetically downstream from Pax3 and is a direct target...
  32. Shin D, Osborne T. FGF15/FGFR4 integrates growth factor signaling with hepatic bile acid metabolism and insulin action. J Biol Chem. 2009;284:11110-20 pubmed publisher
    ..X receptor) activates expression of fibroblast growth factor (FGF) 15 in the intestine, which acts through hepatic FGFR4 to suppress cholesterol-7alpha hydroxylase (CYP7A1) and limit bile acid production...
  33. 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. ..
  34. Ford Perriss M, Guimond S, Greferath U, Kita M, Grobe K, Habuchi H, et al. Variant heparan sulfates synthesized in developing mouse brain differentially regulate FGF signaling. Glycobiology. 2002;12:721-7 pubmed
  35. Kwiatkowski B, Kirillova I, Richard R, Israeli D, Yablonka Reuveni Z. FGFR4 and its novel splice form in myogenic cells: Interplay of glycosylation and tyrosine phosphorylation. J Cell Physiol. 2008;215:803-17 pubmed publisher
    The family of fibroblast growth factor receptors (FGFRs) is encoded by four distinct genes. FGFR1 and FGFR4 are both expressed during myogenesis, but whereas the function of FGFR1 in myoblast proliferation has been documented, the role ..
  36. Potthoff M, Bonéy Montoya J, Choi M, He T, Sunny N, Satapati S, et al. FGF15/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1? pathway. Cell Metab. 2011;13:729-38 pubmed publisher
    ..Overexpression of PGC-1? blocks the inhibitory effect of FGF15/19 on gluconeogenic gene expression. These results demonstrate that FGF15/19 works subsequent to insulin as a postprandial regulator of hepatic carbohydrate homeostasis. ..
  37. van Heumen W, Claxton C, Pickles J. Fibroblast growth factor receptor-4 splice variants cause deletion of a critical tyrosine. IUBMB Life. 1999;48:73-8 pubmed
    We have identified two novel isoforms of fibroblast growth factor receptor-4 (FGFR4). They result from alternative splicing of intron 17. Two transcripts, both slightly larger than the one coding for the known mouse FGFR4, are generated...
  38. Marshall A, van der Ent M, Grosveld G. PAX3-FOXO1 and FGFR4 in alveolar rhabdomyosarcoma. Mol Carcinog. 2012;51:807-15 pubmed publisher
    ..We hypothesized fibroblast growth factor receptor 4 (FGFR4) may act as an effector of PAX3-FOXO1, contributing to PAX3-FOXO1 tumorigenic phenotypes...
  39. Cool S, Jackson R, Pincus P, Dickinson I, Nurcombe V. Fibroblast growth factor receptor 4 (FGFR4) expression in newborn murine calvaria and primary osteoblast cultures. Int J Dev Biol. 2002;46:519-23 pubmed
    ..Although mutations in FGFR1, 2, and 3 genes are known to cause skeletal deformities, the expression of FGFR4 in bony tissue remains unclear...
  40. Murakami M, Nguyen L, Hatanaka K, Schachterle W, Chen P, Zhuang Z, et al. FGF-dependent regulation of VEGF receptor 2 expression in mice. J Clin Invest. 2011;121:2668-78 pubmed publisher
    ..Thus, basal FGF stimulation of the endothelium is required for maintenance of VEGFR2 expression and the ability to respond to VEGF stimulation and accounts for the hierarchic control of vascular formation by FGFs and VEGF. ..
  41. Bowles J, Feng C, Spiller C, Davidson T, Jackson A, Koopman P. FGF9 suppresses meiosis and promotes male germ cell fate in mice. Dev Cell. 2010;19:440-9 pubmed publisher
  42. Hayashi T, Ray C, Younkins C, Bermingham McDonogh O. Expression patterns of FGF receptors in the developing mammalian cochlea. Dev Dyn. 2010;239:1019-26 pubmed publisher
    ..5 through postnatal ages. We find that Fgfr1, 2, and 3 are expressed in the epithelium of the cochlear duct and Fgfr4 is limited in its expression to the mesenchyme surrounding the duct...
  43. Li C, Scott D, Hatch E, Tian X, Mansour S. Dusp6 (Mkp3) is a negative feedback regulator of FGF-stimulated ERK signaling during mouse development. Development. 2007;134:167-76 pubmed
  44. Iseki S, Wilkie A, Morriss Kay G. Fgfr1 and Fgfr2 have distinct differentiation- and proliferation-related roles in the developing mouse skull vault. Development. 1999;126:5611-20 pubmed
  45. Goetz R, Nakada Y, Hu M, Kurosu H, Wang L, Nakatani T, et al. Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23-FGFR-Klotho complex formation. Proc Natl Acad Sci U S A. 2010;107:407-12 pubmed publisher
    ..We propose that peptides derived from the C-terminal tail of FGF23 or peptidomimetics and small-molecule organomimetics of the C-terminal tail can be used as therapeutics to treat renal phosphate wasting. ..
  46. Rappolee D, Patel Y, Jacobson K. Expression of fibroblast growth factor receptors in peri-implantation mouse embryos. Mol Reprod Dev. 1998;51:254-64 pubmed
    ..The data suggest roles for FGFR-3 and FGFR-4 in peri-implantation development. ..
  47. Yu C, Wang F, Jin C, Wu X, Chan W, McKeehan W. Increased carbon tetrachloride-induced liver injury and fibrosis in FGFR4-deficient mice. Am J Pathol. 2002;161:2003-10 pubmed
    ..Recently, we showed that mice in which FGFR4 was ablated from the germline exhibited elevated cholesterol metabolism and bile acid synthesis coincident with ..
  48. Chi L, Zhang S, Lin Y, Prunskaite Hyyryläinen R, Vuolteenaho R, Itäranta P, et al. Sprouty proteins regulate ureteric branching by coordinating reciprocal epithelial Wnt11, mesenchymal Gdnf and stromal Fgf7 signalling during kidney development. Development. 2004;131:3345-56 pubmed
    ..Together, these data suggest that Spry genes contribute to reciprocal epithelial-mesenchymal and stromal signalling controlling ureteric branching, which involves the coordination of Ffg/Wnt11/Gdnf pathways. ..
  49. Yu C, Wang F, Jin C, Huang X, McKeehan W. Independent repression of bile acid synthesis and activation of c-Jun N-terminal kinase (JNK) by activated hepatocyte fibroblast growth factor receptor 4 (FGFR4) and bile acids. J Biol Chem. 2005;280:17707-14 pubmed
    ..FGF receptor 4 (FGFR4) is the sole FGFR receptor kinase that is significantly expressed in mature hepatocytes...
  50. Li H, Martin A, David V, Quarles L. Compound deletion of Fgfr3 and Fgfr4 partially rescues the Hyp mouse phenotype. Am J Physiol Endocrinol Metab. 2011;300:E508-17 pubmed publisher
    ..the Hyp mouse model, which displays FGF23-mediated hypophosphatemia and aberrant vitamin D, deletion of Fgfr3 or Fgfr4 alone failed to correct the Hyp phenotype...
  51. Park M, Rieger Fackeldey E, Schanbacher B, Cook A, Bauer J, Rogers L, et al. Altered expressions of fibroblast growth factor receptors and alveolarization in neonatal mice exposed to 85% oxygen. Pediatr Res. 2007;62:652-7 pubmed
    ..The temporally and spatially specific alterations in the expressions of FGFR-3, FGFR-4, and FGF-7 in the mice exposed to hyperoxia may contribute to aberrant lung development. ..
  52. Korhonen J, Partanen J, Alitalo K. Expression of FGFR-4 mRNA in developing mouse tissues. Int J Dev Biol. 1992;36:323-9 pubmed
    ..In addition, the developing metanephros contains FGFR-4 transcripts. These results suggest that FGFR-4 may be particularly important for the differentiation of skeletal muscle and endodermally derived organs. ..