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Gene Review

FGF2  -  fibroblast growth factor 2 (basic)

Homo sapiens

Synonyms: BFGF, Basic fibroblast growth factor, FGF-2, FGFB, Fibroblast growth factor 2, ...
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Disease relevance of FGF2


Psychiatry related information on FGF2


High impact information on FGF2


Chemical compound and disease context of FGF2


Biological context of FGF2


Anatomical context of FGF2

  • To elucidate the mechanism by which these substitutions cause AS, we determined the crystal structures of these two FGFR2 mutants in complex with fibroblast growth factor 2 (FGF2) [25].
  • Ectopic expression of FGF3 also influences the formation of the normal orthotopic inner ear, whereas another member of the FGF family, FGF2, shows no effects on inner ear induction [26].
  • Here, we evaluated the effects of different heparan sulfate proteoglycan (HSPG)-expressing cell lines and HSPGs derived from these cells on FGF2-induced FGFR1-phosphorylation in heparan sulfate-negative BaF3 cells [27].
  • When both conventional and novel PKCs expressed by RCS chondrocytes (PKCalpha, -gamma, -delta, and -epsilon) were down-regulated by phorbol ester, cells remained responsive to FGF2 with Erk activation, and this activation was sensitive to Bis I [3].
  • Myoblast C2C12 cells cultured in the presence of FGF2 actively proliferate and showed a differentiation-defective phenotype compared with cells cultured in low serum or in the presence of insulin [28].

Associations of FGF2 with chemical compounds

  • Finally, we have shown that peptide A5G27 directly blocks FGF2 binding to heparin [1].
  • With EGF plus FGF2 for 14 days, some BrdU-positive cells in the ependyma also expressed nestin [29].
  • A 24 to 48-hr stimulation with pro-inflammatory cytokines, TGF-beta and FGF2 induced a significant increase in the concentrations of all integrin chains [30].
  • Neural stem cells from neurogenic regions of mammalian CNS are clonogenic in an in vitro culture system exploiting serum and anchorage withdrawal in medium supplemented with methyl cellulose and the pleiotropic growth factors EGF, FGF2, and insulin [31].
  • This upregulation could be abrogated by pretreatment with the protein synthesis inhibitor cycloheximide, suggesting that the upregulation of syndecan-4 by FGF2 is not a primary response [32].
  • FGF-2 stimulated DU-145 cell proliferation, whereas neither FGF-2 nor fibrinogen affected the growth of PC-3 or A549 cells [33].
  • This data suggests that potent mitogenic signaling results from heparin-mediated trans-dimerization of FGF2, consistent with the asymmetric model of ternary complex formation [34].

Physical interactions of FGF2


Enzymatic interactions of FGF2

  • Down-regulation of perlecan expression by cleaved and latent antithrombins was observed in both basic fibroblast growth factor (bFGF)-stimulated and unstimulated cells, whereas the antiangiogenic antithrombins inhibited the proliferation of only bFGF-stimulated HUVECs by arresting cells at the G(1) cell cycle phase [40].
  • In addition, Nck-associated proteins are highly tyrosine phosphorylated and JNK reaches a higher level of activation when FGF-2 triggers DNA synthesis [41].
  • In IMR-90 and WI-38 cells, serum or basic fibroblast growth factor induces an increase in the amount of hyperphosphorylated forms of RB protein in a manner strictly dependent on [Ca]out [42].

Regulatory relationships of FGF2


Other interactions of FGF2


Analytical, diagnostic and therapeutic context of FGF2

  • Furthermore the FGF2-induced osteogenic response in the mouse calvarial organ culture system was blocked by the soluble FGFR2IIIcS252W [53].
  • Using a complementary DNA microarray containing 4451 cancer-related, sequence-verified features, we identified a subset of EOC characterized by the expression of numerous genes related to the extracellular matrix (ECM) and its remodeling, along with elements of the fibroblast growth factor 2 (FGF2) signaling pathway [54].
  • Integrin expression was assessed by qualitative methods (immunocytochemistry, Western blotting) and semi-quantitative techniques (FACS, cellular ELISA), before and after stimulation by TNFalpha, IL1-beta, TGF-beta, FGF2, interferon gamma and interferon alpha-2b [30].
  • In situ hybridization analysis confirmed that in contrast to FGF1 and FGF2, expression of FGF21 mRNA was limited to hepatocytes [55].
  • Methods and results: Wildtype, Fgf2 KO (absence of all FGF2 isoforms) and FGF2 LMWKO (absence of LMW isoform) hearts were subjected to an ex vivo work-performing heart ischemic model of 60 min ischemia and 120 min reperfusion [56].


  1. Laminin alpha5 chain metastasis- and angiogenesis-inhibiting peptide blocks fibroblast growth factor 2 activity by binding to the heparan sulfate chains of CD44. Hibino, S., Shibuya, M., Hoffman, M.P., Engbring, J.A., Hossain, R., Mochizuki, M., Kudoh, S., Nomizu, M., Kleinman, H.K. Cancer Res. (2005) [Pubmed]
  2. Heparin affin regulatory peptide/pleiotrophin mediates fibroblast growth factor 2 stimulatory effects on human prostate cancer cells. Hatziapostolou, M., Polytarchou, C., Katsoris, P., Courty, J., Papadimitriou, E. J. Biol. Chem. (2006) [Pubmed]
  3. Bisindolylmaleimide I Suppresses Fibroblast Growth Factor-mediated Activation of Erk MAP Kinase in Chondrocytes by Preventing Shp2 Association with the Frs2 and Gab1 Adaptor Proteins. Krejci, P., Masri, B., Salazar, L., Farrington-Rock, C., Prats, H., Thompson, L.M., Wilcox, W.R. J. Biol. Chem. (2007) [Pubmed]
  4. Fibroblast growth factor (FGF) soluble receptor 1 acts as a natural inhibitor of FGF2 neurotrophic activity during retinal degeneration. Guillonneau, X., Régnier-Ricard, F., Laplace, O., Jonet, L., Bryckaert, M., Courtois, Y., Mascarelli, F. Mol. Biol. Cell (1998) [Pubmed]
  5. Human primitive neuroectodermal tumour cells behave as multipotent neural precursors in response to FGF2. Derrington, E.A., Dufay, N., Rudkin, B.B., Belin, M.F. Oncogene (1998) [Pubmed]
  6. Critical periods of basic fibroblast growth factor and brain-derived neurotrophic factor in the development of the chicken cochleovestibular ganglion in vitro. Hossain, W.A., Rutledge, A., Morest, D.K. Exp. Neurol. (1997) [Pubmed]
  7. Acidic and basic fibroblast growth factor-like immunoreactivity in the striatum and midbrain in Huntington's disease. Tooyama, I., Kremer, H.P., Hayden, M.R., Kimura, H., McGeer, E.G., McGeer, P.L. Brain Res. (1993) [Pubmed]
  8. Increased immunoreactivity for Jun- and Fos-related proteins in Alzheimer's disease: association with pathology. Anderson, A.J., Cummings, B.J., Cotman, C.W. Exp. Neurol. (1994) [Pubmed]
  9. Overexpression of nerve growth factor and basic fibroblast growth factor in AIDS dementia complex. Boven, L.A., Middel, J., Portegies, P., Verhoef, J., Jansen, G.H., Nottet, H.S. J. Neuroimmunol. (1999) [Pubmed]
  10. Trophic factors in cerebrospinal fluid and spinal cord of patients with tropical spastic paraparesis, HIV, and Creutzfeldt-Jakob disease. Albrecht, D., García, L., Cartier, L., Kettlun, A.M., Vergara, C., Collados, L., Valenzuela, M.A. AIDS Res. Hum. Retroviruses (2006) [Pubmed]
  11. Perlecan, basal lamina proteoglycan, promotes basic fibroblast growth factor-receptor binding, mitogenesis, and angiogenesis. Aviezer, D., Hecht, D., Safran, M., Eisinger, M., David, G., Yayon, A. Cell (1994) [Pubmed]
  12. Release of an inhibitor of angiogenesis upon induction of wild type p53 expression in glioblastoma cells. Van Meir, E.G., Polverini, P.J., Chazin, V.R., Su Huang, H.J., de Tribolet, N., Cavenee, W.K. Nat. Genet. (1994) [Pubmed]
  13. N-CoR controls differentiation of neural stem cells into astrocytes. Hermanson, O., Jepsen, K., Rosenfeld, M.G. Nature (2002) [Pubmed]
  14. Maspin is an angiogenesis inhibitor. Zhang, M., Volpert, O., Shi, Y.H., Bouck, N. Nat. Med. (2000) [Pubmed]
  15. Tumor-host interactions in the gallbladder suppress distal angiogenesis and tumor growth: involvement of transforming growth factor beta1. Gohongi, T., Fukumura, D., Boucher, Y., Yun, C.O., Soff, G.A., Compton, C., Todoroki, T., Jain, R.K. Nat. Med. (1999) [Pubmed]
  16. Identification of FGF receptor-binding peptides for cancer gene therapy. Maruta, F., Parker, A.L., Fisher, K.D., Hallissey, M.T., Ismail, T., Rowlands, D.C., Chandler, L.A., Kerr, D.J., Seymour, L.W. Cancer Gene Ther. (2002) [Pubmed]
  17. Inflammatory cytokines synergize with the HIV-1 Tat protein to promote angiogenesis and Kaposi's sarcoma via induction of basic fibroblast growth factor and the alpha v beta 3 integrin. Barillari, G., Sgadari, C., Palladino, C., Gendelman, R., Caputo, A., Morris, C.B., Nair, B.C., Markham, P., Nel, A., Stürzl, M., Ensoli, B. J. Immunol. (1999) [Pubmed]
  18. Phosphorothioate antisense oligonucleotides against basic fibroblast growth factor inhibit anchorage-dependent and anchorage-independent growth of a malignant glioblastoma cell line. Murphy, P.R., Sato, Y., Knee, R.S. Mol. Endocrinol. (1992) [Pubmed]
  19. Expression of the nucleoside triphosphate pyrophosphohydrolase PC-1 is induced by basic fibroblast growth factor (bFGF) and modulated by activation of the protein kinase A and C pathways in osteoblast-like osteosarcoma cells. Solan, J.L., Deftos, L.J., Goding, J.W., Terkeltaub, R.A. J. Bone Miner. Res. (1996) [Pubmed]
  20. High plasma basic fibroblast growth factor concentration is associated with response to thalidomide in progressive multiple myeloma. Neben, K., Moehler, T., Egerer, G., Kraemer, A., Hillengass, J., Benner, A., Ho, A.D., Goldschmidt, H. Clin. Cancer Res. (2001) [Pubmed]
  21. Signaling by fibroblast growth factors (FGF) and fibroblast growth factor receptor 2 (FGFR2)-activating mutations blocks mineralization and induces apoptosis in osteoblasts. Mansukhani, A., Bellosta, P., Sahni, M., Basilico, C. J. Cell Biol. (2000) [Pubmed]
  22. Regulation of alphaA-crystallin via Pax6, c-Maf, CREB and a broad domain of lens-specific chromatin. Yang, Y., Stopka, T., Golestaneh, N., Wang, Y., Wu, K., Li, A., Chauhan, B.K., Gao, C.Y., Cveklová, K., Duncan, M.K., Pestell, R.G., Chepelinsky, A.B., Skoultchi, A.I., Cvekl, A. EMBO J. (2006) [Pubmed]
  23. A Ser(365)-->Cys mutation of fibroblast growth factor receptor 3 in mouse downregulates Ihh/PTHrP signals and causes severe achondroplasia. Chen, L., Li, C., Qiao, W., Xu, X., Deng, C. Hum. Mol. Genet. (2001) [Pubmed]
  24. Apert syndrome mutations in fibroblast growth factor receptor 2 exhibit increased affinity for FGF ligand. Anderson, J., Burns, H.D., Enriquez-Harris, P., Wilkie, A.O., Heath, J.K. Hum. Mol. Genet. (1998) [Pubmed]
  25. Structural basis for fibroblast growth factor receptor 2 activation in Apert syndrome. Ibrahimi, O.A., Eliseenkova, A.V., Plotnikov, A.N., Yu, K., Ornitz, D.M., Mohammadi, M. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  26. Induction of inner ear fate by FGF3. Vendrell, V., Carnicero, E., Giraldez, F., Alonso, M.T., Schimmang, T. Development (2000) [Pubmed]
  27. Membrane heparan sulfate proteoglycan-supported FGF2-FGFR1 signaling: evidence in support of the "cooperative end structures" model. Zhang, Z., Coomans, C., David, G. J. Biol. Chem. (2001) [Pubmed]
  28. Sprouty-2 overexpression in C2C12 cells confers myogenic differentiation properties in the presence of FGF2. de Alvaro, C., Martinez, N., Rojas, J.M., Lorenzo, M. Mol. Biol. Cell (2005) [Pubmed]
  29. Epidermal growth factor and fibroblast growth factor 2 cause proliferation of ependymal precursor cells in the adult rat spinal cord in vivo. Kojima, A., Tator, C.H. J. Neuropathol. Exp. Neurol. (2000) [Pubmed]
  30. alpha6beta1 integrin expression in hepatocarcinoma cells: regulation and role in cell adhesion and migration. Nejjari, M., Hafdi, Z., Dumortier, J., Bringuier, A.F., Feldmann, G., Scoazec, J.Y. Int. J. Cancer (1999) [Pubmed]
  31. Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro. Ignatova, T.N., Kukekov, V.G., Laywell, E.D., Suslov, O.N., Vrionis, F.D., Steindler, D.A. Glia (2002) [Pubmed]
  32. Regulated expression of syndecan-4 in rat calvaria osteoblasts induced by fibroblast growth factor-2. Song, S.J., Cool, S.M., Nurcombe, V. J. Cell. Biochem. (2007) [Pubmed]
  33. Fibrinogen synthesized by cancer cells augments the proliferative effect of fibroblast growth factor-2 (FGF-2). Sahni, A., Simpson-Haidaris, P.J., Sahni, S.K., Vaday, G.G., Francis, C.W. J. Thromb. Haemost. (2008) [Pubmed]
  34. Evidence that heparin saccharides promote FGF2 mitogenesis through two distinct mechanisms. Goodger, S.J., Robinson, C.J., Murphy, K.J., Gasiunas, N., Harmer, N.J., Blundell, T.L., Pye, D.A., Gallagher, J.T. J. Biol. Chem. (2008) [Pubmed]
  35. Heterodimerization of FGF-receptor 1 and PDGF-receptor-alpha: a novel mechanism underlying the inhibitory effect of PDGF-BB on FGF-2 in human cells. Faraone, D., Aguzzi, M.S., Ragone, G., Russo, K., Capogrossi, M.C., Facchiano, A. Blood (2006) [Pubmed]
  36. BMP-2 augments FGF-induced differentiation of PC12 cells through upregulation of FGF receptor-1 expression. Hayashi, H., Ishisaki, A., Suzuki, M., Imamura, T. J. Cell. Sci. (2001) [Pubmed]
  37. Plasmin-mediated fibroblast growth factor-2 mobilisation supports smooth muscle cell proliferation in human saphenous vein. George, S.J., Johnson, J.L., Smith, M.A., Jackson, C.L. J. Vasc. Res. (2001) [Pubmed]
  38. Fibroblast growth factor-2 interacts with free ribosomal protein S19. Soulet, F., Al Saati, T., Roga, S., Amalric, F., Bouche, G. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  39. Identification of an antiangiogenic FGF2-binding site in the N terminus of the soluble pattern recognition receptor PTX3. Camozzi, M., Rusnati, M., Bugatti, A., Bottazzi, B., Mantovani, A., Bastone, A., Inforzato, A., Vincenti, S., Bracci, L., Mastroianni, D., Presta, M. J. Biol. Chem. (2006) [Pubmed]
  40. Antiangiogenic antithrombin down-regulates the expression of the proangiogenic heparan sulfate proteoglycan, perlecan, in endothelial cells. Zhang, W., Chuang, Y.J., Swanson, R., Li, J., Seo, K., Leung, L., Lau, L.F., Olson, S.T. Blood (2004) [Pubmed]
  41. Functional Rac-1 and Nck signaling networks are required for FGF-2-induced DNA synthesis in MCF-7 cells. Liu, J.F., Chevet, E., Kebache, S., Lemaitre, G., Barritault, D., Larose, L., Crépin, M. Oncogene (1999) [Pubmed]
  42. Ca(2+)-dependent stimulation of retinoblastoma gene product phosphorylation and p34cdc2 kinase activation in serum-stimulated human fibroblasts. Takuwa, N., Zhou, W., Kumada, M., Takuwa, Y. J. Biol. Chem. (1993) [Pubmed]
  43. Basic fibroblast growth factor inhibits the anabolic activity of insulin-like growth factor 1 and osteogenic protein 1 in adult human articular chondrocytes. Loeser, R.F., Chubinskaya, S., Pacione, C., Im, H.J. Arthritis Rheum. (2005) [Pubmed]
  44. Basic fibroblast growth factor suppresses p53 activation in the neoplastic cells of a proportion of patients with chronic lymphocytic leukaemia. Romanov, V.V., James, C.H., Sherrington, P.D., Pettitt, A.R. Oncogene (2005) [Pubmed]
  45. Human chondrosarcoma secretes vascular endothelial growth factor to induce tumor angiogenesis and stores basic fibroblast growth factor for regulation of its own growth. Furumatsu, T., Nishida, K., Kawai, A., Namba, M., Inoue, H., Ninomiya, Y. Int. J. Cancer (2002) [Pubmed]
  46. TGF-beta 1 induces proliferation in human renal fibroblasts via induction of basic fibroblast growth factor (FGF-2). Strutz, F., Zeisberg, M., Renziehausen, A., Raschke, B., Becker, V., van Kooten, C., Müller, G. Kidney Int. (2001) [Pubmed]
  47. Androgen receptor protein is down-regulated by basic fibroblast growth factor in prostate cancer cells. Cronauer, M.V., Nessler-Menardi, C., Klocker, H., Maly, K., Hobisch, A., Bartsch, G., Culig, Z. Br. J. Cancer (2000) [Pubmed]
  48. During angiogenesis, vascular endothelial growth factor and basic fibroblast growth factor regulate natural killer cell adhesion to tumor endothelium. Melder, R.J., Koenig, G.C., Witwer, B.P., Safabakhsh, N., Munn, L.L., Jain, R.K. Nat. Med. (1996) [Pubmed]
  49. Suppression of endothelin-1-induced mitogenic responses of human aortic smooth muscle cells by interleukin-1 beta. Fujitani, Y., Ninomiya, H., Okada, T., Urade, Y., Masaki, T. J. Clin. Invest. (1995) [Pubmed]
  50. Fibroblast growth factor 2 and transforming growth factor beta 1 interactions in human liver myofibroblasts. Rosenbaum, J., Blazejewski, S., Préaux, A.M., Mallat, A., Dhumeaux, D., Mavier, P. Gastroenterology (1995) [Pubmed]
  51. Angiogenesis as a novel component of inflammatory bowel disease pathogenesis. Danese, S., Sans, M., de la Motte, C., Graziani, C., West, G., Phillips, M.H., Pola, R., Rutella, S., Willis, J., Gasbarrini, A., Fiocchi, C. Gastroenterology (2006) [Pubmed]
  52. Estrogen stimulates delayed mitogen-activated protein kinase activity in human endothelial cells via an autocrine loop that involves basic fibroblast growth factor. Kim-Schulze, S., Lowe, W.L., Schnaper, H.W. Circulation (1998) [Pubmed]
  53. A soluble form of fibroblast growth factor receptor 2 (FGFR2) with S252W mutation acts as an efficient inhibitor for the enhanced osteoblastic differentiation caused by FGFR2 activation in Apert syndrome. Tanimoto, Y., Yokozeki, M., Hiura, K., Matsumoto, K., Nakanishi, H., Matsumoto, T., Marie, P.J., Moriyama, K. J. Biol. Chem. (2004) [Pubmed]
  54. Gene expression profiling of advanced ovarian cancer: characterization of a molecular signature involving fibroblast growth factor 2. De Cecco, L., Marchionni, L., Gariboldi, M., Reid, J.F., Lagonigro, M.S., Caramuta, S., Ferrario, C., Bussani, E., Mezzanzanica, D., Turatti, F., Delia, D., Daidone, M.G., Oggionni, M., Bertuletti, N., Ditto, A., Raspagliesi, F., Pilotti, S., Pierotti, M.A., Canevari, S., Schneider, C. Oncogene (2004) [Pubmed]
  55. Forced expression of hepatocyte-specific fibroblast growth factor 21 delays initiation of chemically induced hepatocarcinogenesis. Huang, X., Yu, C., Jin, C., Yang, C., Xie, R., Cao, D., Wang, F., McKeehan, W.L. Mol. Carcinog. (2006) [Pubmed]
  56. The cardioprotective effect of the low molecular weight isoform of fibroblast growth factor-2: The role of JNK signaling. Liao, S., Porter, D., Scott, A., Newman, G., Doetschman, T., Schultz, J.e.l. .J. J. Mol. Cell. Cardiol. (2007) [Pubmed]
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