fibroblast growth factor receptors


Summary: Specific molecular sites or structures on cell membranes that react with FIBROBLAST GROWTH FACTORS (both the basic and acidic forms), their analogs, or their antagonists to elicit or to inhibit the specific response of the cell to these factors. These receptors frequently possess tyrosine kinase activity.

Top Publications

  1. Hellingman C, Koevoet W, Kops N, Farrell E, Jahr H, Liu W, et al. Fibroblast growth factor receptors in in vitro and in vivo chondrogenesis: relating tissue engineering using adult mesenchymal stem cells to embryonic development. Tissue Eng Part A. 2010;16:545-56 pubmed publisher
    ..In embryonic limb development, fibroblast growth factor receptors (FGFRs) play a role in chondrogenic differentiation...
  2. Yu S, Burkhardt M, Nowak M, Ries J, Petrášek Z, Scholpp S, et al. Fgf8 morphogen gradient forms by a source-sink mechanism with freely diffusing molecules. Nature. 2009;461:533-6 pubmed publisher
    ..Our results demonstrate that a freely diffusing morphogen can set up concentration gradients in a complex multicellular tissue by a simple source-sink mechanism. ..
  3. Zakrzewska M, Krowarsch D, Wiedlocha A, Olsnes S, Otlewski J. Highly stable mutants of human fibroblast growth factor-1 exhibit prolonged biological action. J Mol Biol. 2005;352:860-75 pubmed
    ..Our results show that engineered stable growth factor variants exhibit enhanced and prolonged activity, which can be advantageous in terms of the potential therapeutic applications of FGF-1. ..
  4. Thisse B, Thisse C. Functions and regulations of fibroblast growth factor signaling during embryonic development. Dev Biol. 2005;287:390-402 pubmed
  5. Dvorak P, Dvorakova D, Koskova S, Vodinska M, Najvirtova M, Krekac D, et al. Expression and potential role of fibroblast growth factor 2 and its receptors in human embryonic stem cells. Stem Cells. 2005;23:1200-11 pubmed
    ..In conclusion from our data, we propose that this endogenous FGF signaling pathway can be implicated in self-renewal or differentiation of hESCs. ..
  6. Woei Ng K, Speicher T, Dombrowski C, Helledie T, Haupt L, Nurcombe V, et al. Osteogenic differentiation of murine embryonic stem cells is mediated by fibroblast growth factor receptors. Stem Cells Dev. 2007;16:305-18 pubmed
    ..In particular, the data indicate that FGFR1 plays a pivotal role in osteoblast lineage determination. ..
  7. Sahadevan K, Darby S, Leung H, Mathers M, Robson C, Gnanapragasam V. Selective over-expression of fibroblast growth factor receptors 1 and 4 in clinical prostate cancer. J Pathol. 2007;213:82-90 pubmed
    b>Fibroblast growth factor receptors (FGFRs) mediate the tumourigenic effects of FGFs in prostate cancer. These receptors are therefore potential therapeutic targets in the development of inhibitors to this pathway...
  8. McCabe K, Shiau C, Bronner Fraser M. Identification of candidate secreted factors involved in trigeminal placode induction. Dev Dyn. 2007;236:2925-35 pubmed
  9. Motomura K, Hagiwara A, Komi Kuramochi A, Hanyu Y, Honda E, Suzuki M, et al. An FGF1:FGF2 chimeric growth factor exhibits universal FGF receptor specificity, enhanced stability and augmented activity useful for epithelial proliferation and radioprotection. Biochim Biophys Acta. 2008;1780:1432-40 pubmed publisher
    ..These results suggest that FGFC could be useful in a variety of clinical applications, including promotion of wound healing and protection against radiation-induced damage. ..

More Information


  1. Eswarakumar V, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005;16:139-49 pubmed
  2. Popovici C, Fallet M, Marguet D, Birnbaum D, Roubin R. Intracellular trafficking of LET-756, a fibroblast growth factor of C. elegans, is controlled by a balance of export and nuclear signals. Exp Cell Res. 2006;312:1484-95 pubmed
    ..We propose that LET-756 exerts its functions through a balance between secreted and nuclear forms due to two opposite addressing signals, (i) synergy of several NLS and (ii) attenuated secretion signal...
  3. Dey J, Bianchi F, Voshol J, Bonenfant D, Oakeley E, Hynes N. Targeting fibroblast growth factor receptors blocks PI3K/AKT signaling, induces apoptosis, and impairs mammary tumor outgrowth and metastasis. Cancer Res. 2010;70:4151-62 pubmed publisher
    ..Of interest are the downregulated matrix metalloproteases (MMP), in particular MMP9, which is essential for metastatic spread of 4T1 tumors. ..
  4. Popovici C, Roubin R, Coulier F, Birnbaum D. An evolutionary history of the FGF superfamily. Bioessays. 2005;27:849-57 pubmed
    ..A second expansion, which took place during euchordate evolution, is associated with genome duplications. It increased the number of members in the families. Subsequent losses reduced that number to the present-day figures. ..
  5. Hynes N, Dey J. Potential for targeting the fibroblast growth factor receptors in breast cancer. Cancer Res. 2010;70:5199-202 pubmed publisher
    ..This review summarizes recent findings on the fibroblast growth factor receptors (FGFR) and the data supporting their role in breast cancer...
  6. Vecchione A, Cooper H, Trim K, Akbarzadeh S, Heath J, Wheldon L. Protein partners in the life history of activated fibroblast growth factor receptors. Proteomics. 2007;7:4565-78 pubmed
    b>Fibroblast growth factor receptors (FGFRs) are a family of four transmembrane (TM) receptor tyrosine kinases (RTKs) which bind to a large family of fibroblast growth factor (FGF) ligands with varying affinity and specificity...
  7. Rusnati M, Presta M. Fibroblast growth factors/fibroblast growth factor receptors as targets for the development of anti-angiogenesis strategies. Curr Pharm Des. 2007;13:2025-44 pubmed
    ..Purpose of this review is to summarize the different modalities that have been approached to impair the pro-angiogenic activity of the FGF/FGF receptor system and discuss their possible therapeutic implications. ..
  8. Haugsten E, Malecki J, Bjørklund S, Olsnes S, Wesche J. Ubiquitination of fibroblast growth factor receptor 1 is required for its intracellular sorting but not for its endocytosis. Mol Biol Cell. 2008;19:3390-403 pubmed publisher
    ..The altered sorting resulted in sustained signaling. The duration of FGFR1 signaling seems to be tightly regulated by receptor ubiquitination and subsequent sorting to the lysosomes for degradation. ..
  9. Delaval B, Letard S, Lelièvre H, Chevrier V, Daviet L, Dubreuil P, et al. Oncogenic tyrosine kinase of malignant hemopathy targets the centrosome. Cancer Res. 2005;65:7231-40 pubmed
    ..This could represent a potential new mechanism of oncogenic transformation occurring specifically at the centrosome. ..
  10. Mohammadi M, Olsen S, Goetz R. A protein canyon in the FGF-FGF receptor dimer selects from an à la carte menu of heparan sulfate motifs. Curr Opin Struct Biol. 2005;15:506-16 pubmed
  11. Zhang X, Ibrahimi O, Olsen S, Umemori H, Mohammadi M, Ornitz D. Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J Biol Chem. 2006;281:15694-700 pubmed
    ..This study completes the mitogenesis-based comparison of receptor specificity of the entire FGF family under standard conditions and should help in interpreting and predicting in vivo biological activity. ..
  12. Kadam S, McMahon A, Tzou P, Stathopoulos A. FGF ligands in Drosophila have distinct activities required to support cell migration and differentiation. Development. 2009;136:739-47 pubmed publisher
    ..We contend that inherent properties of FGF ligands make them suitable to support specific FGF-dependent processes, and that FGF ligands are not always interchangeable. ..
  13. Srisuma S, Bhattacharya S, Simon D, Solleti S, Tyagi S, Starcher B, et al. Fibroblast growth factor receptors control epithelial-mesenchymal interactions necessary for alveolar elastogenesis. Am J Respir Crit Care Med. 2010;181:838-50 pubmed publisher
    ..Epithelial/mesenchymal signaling mechanisms appear to contribute to FGFR-dependent alveolar elastogenesis and proper airspace formation. ..
  14. Delaval B, Lelievre H, Birnbaum D. Myeloproliferative disorders: the centrosome connection. Leukemia. 2005;19:1739-44 pubmed
    ..The same effect might be triggered by other fusion kinases in other MPD and non-MPD malignancies. ..
  15. Kang H, Kim J, Kwon H, Nam K, Youn H, Sok D, et al. Basic fibroblast growth factor activates ERK and induces c-fos in human embryonic stem cell line MizhES1. Stem Cells Dev. 2005;14:395-401 pubmed
    ..mRNA and protein levels of the c-fos gene were increased by bFGF. Induction of c-Fos was dependent on MEKl. Therefore, it is likely that bFGF contributes to maintenance of human ES cells, at least in part, through the MEK1/ERK pathway. ..
  16. Rosenthal R, Malek G, Salomon N, Peill Meininghaus M, Coeppicus L, Wohlleben H, et al. The fibroblast growth factor receptors, FGFR-1 and FGFR-2, mediate two independent signalling pathways in human retinal pigment epithelial cells. Biochem Biophys Res Commun. 2005;337:241-7 pubmed
    ..Our findings support the hypothesis that there are two different FGFR-1- and FGFR-2-dependent pathways that modulate the role of bFGF in induction of neovascularisation in AMD. ..
  17. Chen G, Forough R. Fibroblast growth factors, fibroblast growth factor receptors, diseases, and drugs. Recent Pat Cardiovasc Drug Discov. 2006;1:211-24 pubmed
    ..Additionally, novel drug development strategies are highlighted and reviewed. ..
  18. Sivak J, Petersen L, Amaya E. FGF signal interpretation is directed by Sprouty and Spred proteins during mesoderm formation. Dev Cell. 2005;8:689-701 pubmed
    ..These differences, combined with the timing of their developmental expression, suggest a mechanism to switch FGFR signal interpretation to coordinate mesoderm formation and cell movements during gastrulation. ..
  19. Grose R, Dickson C. Fibroblast growth factor signaling in tumorigenesis. Cytokine Growth Factor Rev. 2005;16:179-86 pubmed
    ..Here, we outline the model systems that demonstrate the potential oncogenic nature of Fgf signaling and summarise recent evidence that implicates aberrant Fgf signaling as important in the natural history of some common human cancers. ..
  20. Mohammadi M, Olsen S, Ibrahimi O. Structural basis for fibroblast growth factor receptor activation. Cytokine Growth Factor Rev. 2005;16:107-37 pubmed
  21. Saarimäki Vire J, Peltopuro P, Lahti L, Naserke T, Blak A, Vogt Weisenhorn D, et al. Fibroblast growth factor receptors cooperate to regulate neural progenitor properties in the developing midbrain and hindbrain. J Neurosci. 2007;27:8581-92 pubmed
    ..We propose a model for regulation of progenitor cell self-renewal and neuronal differentiation by combinatorial intercellular signals in the ventral midbrain. ..
  22. Stavridis M, Lunn J, Collins B, Storey K. A discrete period of FGF-induced Erk1/2 signalling is required for vertebrate neural specification. Development. 2007;134:2889-94 pubmed
  23. Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, et al. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature. 2006;444:770-4 pubmed
    ..Thus, the concerted action of Klotho and FGFR1(IIIc) reconstitutes the FGF23 receptor. These findings provide insights into the diversity and specificity of interactions between FGF and FGF receptors. ..
  24. Davidson D, Blanc A, Filion D, Wang H, Plut P, Pfeffer G, et al. Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis. J Biol Chem. 2005;280:20509-15 pubmed
    ..This work, thus, identifies FGF18 and FGFR3 as potential molecular targets for intervention in tissue engineering aimed at cartilage repair and regeneration of damaged cartilage. ..
  25. Kwabi Addo B, Ozen M, Ittmann M. The role of fibroblast growth factors and their receptors in prostate cancer. Endocr Relat Cancer. 2004;11:709-24 pubmed
    ..A number of approaches that could target FGF receptors and/or FGF receptor signaling in prostate cancer are currently being developed. ..
  26. Walz C, Chase A, Schoch C, Weisser A, Schlegel F, Hochhaus A, et al. The t(8;17)(p11;q23) in the 8p11 myeloproliferative syndrome fuses MYO18A to FGFR1. Leukemia. 2005;19:1005-9 pubmed
    ..MYO18A-FGFR1 is structurally similar to other fusion tyrosine kinases and is likely to be the causative transforming lesion in this unusual MDS/MPD. ..
  27. Zhao H, Kegg H, Grady S, Truong H, Robinson M, Baum M, et al. Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud. Dev Biol. 2004;276:403-15 pubmed
    ..In conclusion, FGFR2, but not FGFR1, appears crucial for ureteric bud branching morphogenesis and stromal mesenchyme patterning. ..
  28. Anteby E, Natanson Yaron S, Hamani Y, Sciaki Y, Goldman Wohl D, Greenfield C, et al. Fibroblast growth factor-10 and fibroblast growth factor receptors 1-4: expression and peptide localization in human decidua and placenta. Eur J Obstet Gynecol Reprod Biol. 2005;119:27-35 pubmed
    ..We hypothesized that fibroblast growth factor-10 (FGF-10) and fibroblast growth factor receptors 1-4 (FGFR 1-4) are expressed in human decidual and placental tissues...
  29. Wiedłocha A, Sørensen V. Signaling, internalization, and intracellular activity of fibroblast growth factor. Curr Top Microbiol Immunol. 2004;286:45-79 pubmed
    ..The role of FGF internalization and the intracellular activity of some FGFs are discussed in the context of the known signaling induced by FGF. ..
  30. St Bernard R, Zheng L, Liu W, Winer D, Asa S, Ezzat S. Fibroblast growth factor receptors as molecular targets in thyroid carcinoma. Endocrinology. 2005;146:1145-53 pubmed
    ..These data indicate a role for FGFR-4 in human thyroid cancer cell progression and provide a rationale for FGFR manipulation as a potentially novel therapeutic approach. ..
  31. Belloni E, Trubia M, Gasparini P, Micucci C, Tapinassi C, Confalonieri S, et al. 8p11 myeloproliferative syndrome with a novel t(7;8) translocation leading to fusion of the FGFR1 and TIF1 genes. Genes Chromosomes Cancer. 2005;42:320-5 pubmed
    ..Thus, our data extend the involvement of FGFR1 in EMS and lend support to the concept that there is a precise correlation between genotype and phenotype in this disease. ..
  32. Chen L, Deng C. Roles of FGF signaling in skeletal development and human genetic diseases. Front Biosci. 2005;10:1961-76 pubmed
    b>Fibroblast growth factor receptors (FGFRs) exist as a gene family of 4 membrane bound receptor tyrosine kinases (FGFR1-4) that mediate signals of at least 22 fibroblast growth factors (FGF1-22)...
  33. Birnbaum D, Popovici C, Roubin R. A pair as a minimum: the two fibroblast growth factors of the nematode Caenorhabditis elegans. Dev Dyn. 2005;232:247-55 pubmed
    ..Phylogenetic and functional studies suggest that LET-756, like vertebrate FGF9, -16, and -20, belongs to the FGF9 family, whereas EGL-17, like vertebrate FGF8, -17, and -18, could be included in the FGF8 family. ..
  34. Schlessinger J. Common and distinct elements in cellular signaling via EGF and FGF receptors. Science. 2004;306:1506-7 pubmed
    ..The differential circuitry of the intracellular networks that are activated by EGFR and FGFR may affect signal specificity and physiological responses. ..
  35. Wilson R, Vogelsang E, Leptin M. FGF signalling and the mechanism of mesoderm spreading in Drosophila embryos. Development. 2005;132:491-501 pubmed
  36. Shakespeare T, Sellitto C, Li L, Rubinos C, Gong X, Srinivas M, et al. Interaction between Connexin50 and mitogen-activated protein kinase signaling in lens homeostasis. Mol Biol Cell. 2009;20:2582-92 pubmed publisher
    ..These results indicate that MAPK signaling specifically modulates coupling mediated by Cx50 and that gap junctional communication and signal transduction pathways may interact in osmotic regulation during postnatal fiber development. ..
  37. Trokovic N, Trokovic R, Partanen J. Fibroblast growth factor signalling and regional specification of the pharyngeal ectoderm. Int J Dev Biol. 2005;49:797-805 pubmed
    ..Our results suggest that Fgfr1 is important for localized signalling in the pharyngeal ectoderm and consequently for normal tissue interactions in the developing second branchial arch...
  38. Ding W, Shi W, Bellusci S, Groffen J, Heisterkamp N, Minoo P, et al. Sprouty2 downregulation plays a pivotal role in mediating crosstalk between TGF-beta1 signaling and EGF as well as FGF receptor tyrosine kinase-ERK pathways in mesenchymal cells. J Cell Physiol. 2007;212:796-806 pubmed
    ..Together, the combined operation of transcriptional and post-translational mechanisms suggests that regulation of Spry2 is a crucial event and emphasizes the important role that Spry2 plays in controlling cell behaviors. ..
  39. Kuslak S, Marker P. Fibroblast growth factor receptor signaling through MEK-ERK is required for prostate bud induction. Differentiation. 2007;75:638-51 pubmed
    ..They also show that signaling by FGFRs through ERK1/2 is required for androgen-induced budding morphogenesis, proliferation, and gene expression during prostate bud induction. ..
  40. Murakami M, Elfenbein A, Simons M. Non-canonical fibroblast growth factor signalling in angiogenesis. Cardiovasc Res. 2008;78:223-31 pubmed
    ..In this review, we will discuss recent findings related to non-canonical FGF signalling with emphasis on the endothelial biology and angiogenesis. ..
  41. Jin Y, Korin Y, Zhang X, Jindra P, Rozengurt E, Reed E. RNA interference elucidates the role of focal adhesion kinase in HLA class I-mediated focal adhesion complex formation and proliferation in human endothelial cells. J Immunol. 2007;178:7911-22 pubmed
    ..This study shows that FAK plays a critical role in class I-induced cell proliferation, cell survival, and focal adhesion assembly in EC and may promote the development of transplant-associated vasculopathy. ..
  42. Chung W, Tsai P. Role of fibroblast growth factor signaling in gonadotropin-releasing hormone neuronal system development. Front Horm Res. 2010;39:37-50 pubmed publisher
  43. Lea R, Papalopulu N, Amaya E, Dorey K. Temporal and spatial expression of FGF ligands and receptors during Xenopus development. Dev Dyn. 2009;238:1467-79 pubmed publisher
    ..Developmental Dynamics 238:1467-1479, 2009. (c) 2009 Wiley-Liss, Inc. ..
  44. Lopez E, Boucherat O, Franco Montoya M, Bourbon J, Delacourt C, Jarreau P. Nitric oxide donor restores lung growth factor and receptor expression in hyperoxia-exposed rat pups. Am J Respir Cell Mol Biol. 2006;34:738-45 pubmed
  45. Yokote H, Fujita K, Jing X, Sawada T, Liang S, Yao L, et al. Trans-activation of EphA4 and FGF receptors mediated by direct interactions between their cytoplasmic domains. Proc Natl Acad Sci U S A. 2005;102:18866-71 pubmed
  46. Terauchi A, Johnson Venkatesh E, Toth A, Javed D, Sutton M, Umemori H. Distinct FGFs promote differentiation of excitatory and inhibitory synapses. Nature. 2010;465:783-7 pubmed publisher
    ..These results demonstrate that specific FGFs act as target-derived presynaptic organizers and help to organize specific presynaptic terminals in the mammalian brain. ..
  47. Manya H, Akasaka Manya K, Endo T. Klotho protein deficiency and aging. Geriatr Gerontol Int. 2010;10 Suppl 1:S80-7 pubmed publisher
    ..The relationship between aging and alpha-klotho protein function is gradually becoming clear. This review covers the recent advance in alpha-klotho protein research. ..
  48. Zhou W, Hur W, McDermott U, Dutt A, Xian W, Ficarro S, et al. A structure-guided approach to creating covalent FGFR inhibitors. Chem Biol. 2010;17:285-95 pubmed publisher
    ..FIIN-1 is a useful probe of FGFR-dependent cellular phenomena and may provide a starting point of the development of therapeutically relevant irreversible inhibitors of wild-type and drug-resistant forms of FGFR kinases. ..
  49. Shi W, Peyrot S, Munro E, Levine M. FGF3 in the floor plate directs notochord convergent extension in the Ciona tadpole. Development. 2009;136:23-8 pubmed publisher
    ..We propose that FGF signaling coordinates CE movements by regulating PCP pathway components such as Dsh...
  50. Fukushima S, Kato S, Maeda M, Shigemori M. Caspase-9 pathway activation by inhibiting endogenous fibroblast growth factor signaling in human glioma cells. Int J Oncol. 2008;32:467-73 pubmed
    ..The suppression of this or other specific anti-apoptotic pathways may lead to genetic or pharmacological manipulations that favorably modulate the malignant behavior of human gliomas. ..
  51. Seandel M, Butler J, Kobayashi H, Hooper A, White I, Zhang F, et al. Generation of a functional and durable vascular niche by the adenoviral E4ORF1 gene. Proc Natl Acad Sci U S A. 2008;105:19288-93 pubmed publisher
  52. Yu L, Saile K, Swartz C, He H, Zheng X, Kissling G, et al. Differential expression of receptor tyrosine kinases (RTKs) and IGF-I pathway activation in human uterine leiomyomas. Mol Med. 2008;14:264-75 pubmed publisher
    ..These data may provide new anti-tumor targets for noninvasive treatment of fibroids. ..
  53. Benseñor L, Kan H, Wang N, Wallrabe H, Davidson L, Cai Y, et al. IQGAP1 regulates cell motility by linking growth factor signaling to actin assembly. J Cell Sci. 2007;120:658-69 pubmed
    ..Based on these observations, we conclude that IQGAP1 links FGF2 signaling to Arp2/3 complex-dependent actin assembly by serving as a binding partner for FGFR1 and as an activator of N-WASP. ..