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Gene Review

FGF1  -  fibroblast growth factor 1 (acidic)

Homo sapiens

Synonyms: AFGF, Acidic fibroblast growth factor, ECGF, ECGF-beta, ECGFA, ...
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Disease relevance of FGF1


Psychiatry related information on FGF1


High impact information on FGF1


Chemical compound and disease context of FGF1

  • Creatinine kinase content of the affected myocardium showed that both fibroblast growth factors 1 and 2 effectively protected against ischemia reperfusion injury (p < 0.01), and that the vasoactive but nonmitogenic form of the FGF1 was equally protective (p < 0.01 versus control + vehicle) [10].
  • Both autocrine and paracrine effects of transfected acidic fibroblast growth factor are involved in the estrogen-independent and antiestrogen-resistant growth of MCF-7 breast cancer cells [11].
  • Retinoblastoma proliferation was monitored by radiolabeled thymidine incorporation or a vital dye-based assay, after addition of FGF-1 with or without inclusion of a specific FGFR1 neutralizing antibody or FGFR1 antisense oligonucleotides [12].
  • METHODS: Formalin fixed and paraffin wax embedded tissues from 15 fibroadenomas and peritumoral normal breasts were investigated for the expression of aFGF and FGFR4 using immunohistochemistry [13].
  • These results provide novel finding that ET-AR in PASMCs in vitro is unresponsive to hypoxia per se but is robustly simulated by tyrosine kinase receptor-associated growth factors (FGF-1, FGF-2, PDGF-BB) that themselves are stimulated by hypoxia in lung [14].

Biological context of FGF1


Anatomical context of FGF1

  • Cooperative dimerization of fibroblast growth factor 1 (FGF1) upon a single heparin saccharide may drive the formation of 2:2:1 FGF1.FGFR2c.heparin ternary complexes [18].
  • FGF1 expression is sufficient to induce in PC12 cells both differentiation and survival [17].
  • FGF7, also called keratinocyte growth factor, was mutated to mimic either FGF1 or FGF2 at two of the putative high contact points termed FGF7-1 and FGF7-2, respectively [19].
  • These FGF1 transcripts can be detected in cultured cells as well as in normal and diseased tissues [16].
  • Last, the ability of amlexanox to inhibit FGF1 release is reversible and correlates with the restoration of the actin cytoskeleton, suggesting a role for the actin cytoskeleton in the FGF1 release pathway [20].

Associations of FGF1 with chemical compounds


Physical interactions of FGF1

  • 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 [21].
  • Indeed, S100A13 is a copper binding protein able to enhance the export of FGF1 in response to stress in vitro and to induce the formation of a multiprotein aggregate responsible for FGF1 release [26].
  • The cross-linked 125I-labeled aFGF-aFGF receptor complex was specifically immunoprecipitated with FLG antipeptide antibodies [27].
  • Cell-free complexes of heparin and recombinant FGFR4 bound FGF-1 and FGF-2 equally [28].
  • In vitro-translated FIBP bound specifically to a fusion protein of maltose-binding protein and aFGF [29].

Enzymatic interactions of FGF1


Regulatory relationships of FGF1

  • In vitro experiments showed that differential expression of FGF receptor isoforms was induced by aFGF, and also by IL-6 and TGF-beta, which are expressed in cardiac allografts during rejection [30].
  • By contrast, FGF1 internalized in cells expressing FGFR4 followed largely the same intracellular pathway as the recycling ligand, transferrin [31].
  • The purpose of the work in this paper was to determine the mechanism involved in FGF-1 induced MT1-MMP expression in prostate carcinoma cells [32].
  • Activation of the chimeric receptor by aFGF induced a stronger and more persistent increase in the tyrosine phosphorylation of cellular proteins than did activation of FGFR-3 alone [33].
  • In some human T cells, FGF-1 can induce signals necessary for production of interleukin-2, a key cytokine required for T cell proliferation [34].

Other interactions of FGF1

  • We have crystallized a complex between human FGF1 and a two-domain extracellular fragment of human FGFR2 [35].
  • Cells overexpressing FGFR3 IIIb showed FGF1-induced proliferation, which was inhibited by the addition of FGFR3 Delta8-10 [36].
  • Subsets of melanoma cell lines also expressed aFGF, FGF-5, and PDGFB [37].
  • FGF2-Heparin co-crystal complex-assisted design of mutants FGF1 and FGF7 with predictable heparin affinities [19].
  • These data suggest that S100A13 may be involved in the assembly of the multiprotein aggregate required for the release of FGF1 and that Cu2+ oxidation may be an essential post-translational intracellular modifier of this process [22].

Analytical, diagnostic and therapeutic context of FGF1


  1. The non-classical export routes: FGF1 and IL-1alpha point the way. Prudovsky, I., Mandinova, A., Soldi, R., Bagala, C., Graziani, I., Landriscina, M., Tarantini, F., Duarte, M., Bellum, S., Doherty, H., Maciag, T. J. Cell. Sci. (2003) [Pubmed]
  2. Construction of a yeast artificial chromosome contig encompassing the human acidic fibroblast growth factor (FGF1) gene: toward the cloning of the ANLL/MDS tumor-suppressor gene. Chiu, I.M., Gilmore, E.C., Liu, Y., Payson, R.A. Genomics (1994) [Pubmed]
  3. 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]
  4. Fibroblast growth factor modulates HIV coreceptor CXCR4 expression by neural cells. HNRC Group. Sanders, V.J., Everall, I.P., Johnson, R.W., Masliah, E. J. Neurosci. Res. (2000) [Pubmed]
  5. Promoter polymorphism in fibroblast growth factor 1 gene increases risk of definite Alzheimer's disease. Yamagata, H., Chen, Y., Akatsu, H., Kamino, K., Ito, J., Yokoyama, S., Yamamoto, T., Kosaka, K., Miki, T., Kondo, I. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  6. Protective effect of acidic fibroblast growth factor against ischemia-induced learning and memory deficits in two tasks in gerbils. Li, A.J., Oomura, Y., Sasaki, K., Suzuki, K., Hori, T. Physiol. Behav. (1999) [Pubmed]
  7. Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity. Plotnikov, A.N., Hubbard, S.R., Schlessinger, J., Mohammadi, M. Cell (2000) [Pubmed]
  8. Heparin-induced oligomerization of FGF molecules is responsible for FGF receptor dimerization, activation, and cell proliferation. Spivak-Kroizman, T., Lemmon, M.A., Dikic, I., Ladbury, J.E., Pinchasi, D., Huang, J., Jaye, M., Crumley, G., Schlessinger, J., Lax, I. Cell (1994) [Pubmed]
  9. Dual mode of signal transduction by externally added acidic fibroblast growth factor. Wiedłocha, A., Falnes, P.O., Madshus, I.H., Sandvig, K., Olsnes, S. Cell (1994) [Pubmed]
  10. Protection of rat myocardium by mitogenic and non-mitogenic fibroblast growth factor during post-ischemic reperfusion. Cuevas, P., Carceller, F., Lozano, R.M., Crespo, A., Zazo, M., Giménez-Gallego, G. Growth Factors (1997) [Pubmed]
  11. Both autocrine and paracrine effects of transfected acidic fibroblast growth factor are involved in the estrogen-independent and antiestrogen-resistant growth of MCF-7 breast cancer cells. Zhang, L., Kharbanda, S., Hanfelt, J., Kern, F.G. Cancer Res. (1998) [Pubmed]
  12. Acidic fibroblast growth factor (FGF-1) and FGF receptor 1 signaling in human Y79 retinoblastoma. Siffroi-Fernandez, S., Cinaroglu, A., Fuhrmann-Panfalone, V., Normand, G., Bugra, K., Sahel, J., Hicks, D. Arch. Ophthalmol. (2005) [Pubmed]
  13. Expression of acidic fibroblast growth factor (aFGF) and fibroblast growth factor receptor 4 (FGFR4) in breast fibroadenomas. La Rosa, S., Sessa, F., Colombo, L., Tibiletti, M.G., Furlan, D., Capella, C. J. Clin. Pathol. (2001) [Pubmed]
  14. Fibroblast growth factor mediates hypoxia-induced endothelin-- a receptor expression in lung artery smooth muscle cells. Li, P., Oparil, S., Sun, J.Z., Thompson, J.A., Chen, Y.F. J. Appl. Physiol. (2003) [Pubmed]
  15. The involvement of heparan sulfate (HS) in FGF1/HS/FGFR1 signaling complex. Wu, Z.L., Zhang, L., Yabe, T., Kuberan, B., Beeler, D.L., Love, A., Rosenberg, R.D. J. Biol. Chem. (2003) [Pubmed]
  16. The small GTPases Ras, Rac, and Cdc42 transcriptionally regulate expression of human fibroblast growth factor 1. Chotani, M.A., Touhalisky, K., Chiu, I.M. J. Biol. Chem. (2000) [Pubmed]
  17. The neurotrophic activity of fibroblast growth factor 1 (FGF1) depends on endogenous FGF1 expression and is independent of the mitogen-activated protein kinase cascade pathway. Renaud, F., Desset, S., Oliver, L., Gimenez-Gallego, G., Van Obberghen, E., Courtois, Y., Laurent, M. J. Biol. Chem. (1996) [Pubmed]
  18. Cooperative dimerization of fibroblast growth factor 1 (FGF1) upon a single heparin saccharide may drive the formation of 2:2:1 FGF1.FGFR2c.heparin ternary complexes. Robinson, C.J., Harmer, N.J., Goodger, S.J., Blundell, T.L., Gallagher, J.T. J. Biol. Chem. (2005) [Pubmed]
  19. FGF2-Heparin co-crystal complex-assisted design of mutants FGF1 and FGF7 with predictable heparin affinities. Wong, P., Burgess, W.H. J. Biol. Chem. (1998) [Pubmed]
  20. Amlexanox reversibly inhibits cell migration and proliferation and induces the Src-dependent disassembly of actin stress fibers in vitro. Landriscina, M., Prudovsky, I., Mouta Carreira, C., Soldi, R., Tarantini, F., Maciag, T. J. Biol. Chem. (2000) [Pubmed]
  21. 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]
  22. Copper induces the assembly of a multiprotein aggregate implicated in the release of fibroblast growth factor 1 in response to stress. Landriscina, M., Bagalá, C., Mandinova, A., Soldi, R., Micucci, I., Bellum, S., Prudovsky, I., Maciag, T. J. Biol. Chem. (2001) [Pubmed]
  23. The effect of in vitro fibroblast growth factors on cell proliferation in pancreas from normal and streptozotocin-treated rats. Ogneva, V., Martinova, Y. Diabetes Res. Clin. Pract. (2002) [Pubmed]
  24. Production and oestrogen regulation of FGF1 in normal and cancer breast cells. El Yazidi, I., Renaud, F., Laurent, M., Courtois, Y., Boilly-Marer, Y. Biochim. Biophys. Acta (1998) [Pubmed]
  25. Direct binding of integrin alphavbeta3 to FGF1 plays a role in FGF1 signaling. Mori, S., Wu, C.Y., Yamaji, S., Saegusa, J., Shi, B., Ma, Z., Kuwabara, Y., Lam, K.S., Isseroff, R.R., Takada, Y.K., Takada, Y. J. Biol. Chem. (2008) [Pubmed]
  26. S100A13, a new marker of angiogenesis in human astrocytic gliomas. Landriscina, M., Schinzari, G., Di Leonardo, G., Quirino, M., Cassano, A., D'Argento, E., Lauriola, L., Scerrati, M., Prudovsky, I., Barone, C. J. Neurooncol. (2006) [Pubmed]
  27. Receptor for acidic fibroblast growth factor is related to the tyrosine kinase encoded by the fms-like gene (FLG). Ruta, M., Burgess, W., Givol, D., Epstein, J., Neiger, N., Kaplow, J., Crumley, G., Dionne, C., Jaye, M., Schlessinger, J. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  28. Specificity for fibroblast growth factors determined by heparan sulfate in a binary complex with the receptor kinase. Kan, M., Wu, X., Wang, F., McKeehan, W.L. J. Biol. Chem. (1999) [Pubmed]
  29. Cloning of an intracellular protein that binds selectively to mitogenic acidic fibroblast growth factor. Kolpakova, E., Wiedłocha, A., Stenmark, H., Klingenberg, O., Falnes, P.O., Olsnes, S. Biochem. J. (1998) [Pubmed]
  30. Modification of alternative messenger RNA splicing of fibroblast growth factor receptors in human cardiac allografts during rejection. Zhao, X.M., Frist, W.H., Yeoh, T.K., Miller, G.G. J. Clin. Invest. (1994) [Pubmed]
  31. Different intracellular trafficking of FGF1 endocytosed by the four homologous FGF receptors. Haugsten, E.M., Sørensen, V., Brech, A., Olsnes, S., Wesche, J. J. Cell. Sci. (2005) [Pubmed]
  32. Fibroblast growth factor-1 transcriptionally induces membrane type-1 matrix metalloproteinase expression in prostate carcinoma cell line. Udayakumar, T.S., Nagle, R.B., Bowden, G.T. Prostate (2004) [Pubmed]
  33. The fibroblast growth factor receptor-1 is necessary for the induction of neurite outgrowth in PC12 cells by aFGF. Lin, H.Y., Xu, J., Ornitz, D.M., Halegoua, S., Hayman, M.J. J. Neurosci. (1996) [Pubmed]
  34. A functional fibroblast growth factor-1 immunoglobulin fusion protein. Dikov, M.M., Reich, M.B., Dworkin, L., Thomas, J.W., Miller, G.G. J. Biol. Chem. (1998) [Pubmed]
  35. 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]
  36. Alternative splicing of fibroblast growth factor receptor 3 produces a secreted isoform that inhibits fibroblast growth factor-induced proliferation and is repressed in urothelial carcinoma cell lines. Tomlinson, D.C., L'Hôte, C.G., Kennedy, W., Pitt, E., Knowles, M.A. Cancer Res. (2005) [Pubmed]
  37. Induction of growth factor RNA expression in human malignant melanoma: markers of transformation. Albino, A.P., Davis, B.M., Nanus, D.M. Cancer Res. (1991) [Pubmed]
  38. Biosynthetic oligosaccharide libraries for identification of protein-binding heparan sulfate motifs. Exploring the structural diversity by screening for fibroblast growth factor (FGF)1 and FGF2 binding. Jemth, P., Kreuger, J., Kusche-Gullberg, M., Sturiale, L., Giménez-Gallego, G., Lindahl, U. J. Biol. Chem. (2002) [Pubmed]
  39. The location of acidic fibroblast growth factor in the breast is dependent on the activity of proteases present in breast cancer tissue. Coope, R.C., Browne, P.J., Yiangou, C., Bansal, G.S., Walters, J., Groome, N., Shousha, S., Johnston, C.L., Coombes, R.C., Gomm, J.J. Br. J. Cancer (1997) [Pubmed]
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