Skip to main content
SpringerLink
Log in

Human Basic Fibroblast Growth Factor: Structure-Function Relationship of an Angiogenic Molecule

  • Chapter
Book cover Angiogenesis

Part of the book series: NATO ASI Series ((NSSA,volume 263))

  • 86 Accesses

Abstract

Basic fibroblast growth factor (bFGF) belongs to the family of the heparin-binding growth factors which includes also acidic FGF and five other gene products (Basilico and Moscatelli, 1992). bFGF exerts various biological activities in vitro and in vivo on different cell types. In particular, bFGF is an angiogenic molecule that induces a set of complex, coordinated responses in cultured endothelial cells, including cell proliferation, chemotaxis, and protease production (Presta et al., 1986). The identification of the functional domains of bFGF appears to be of pivotal importance for the development of drugs aimed to stimulate or to inhibit angiogenesis in various pathological conditions. In the present paper we will summarize findings from different laboratories on the structure-function relationship of this angiogenic growth factor.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Akiyama, S.K., and Yamada, K.M., 1985, Synthetic peptides competitively inhibit both direct binding to fibroblasts and functional biological assays for the purified cell-binding domain of fibronectin, J. Biol. Chem., 260: 10402.

    PubMed  CAS  Google Scholar 

  • Baird, A., Schubert, D., Ling, N., and Guillemin, R, 1988, Receptor-and heparin-binding domains of basic fibroblast growth factor, Proc. Natl. Acad. Sci. U.S.A. 85: 23–24.

    Article  Google Scholar 

  • Baldin, V., Roman, A.M., Bosc-Bieme, I., Amalric, F., and Bouche, G., 1990, Translocation of bFGF to the nucleus is G1 phase cell cycle specific in bovine aortic endothelial cells, EMBO J. 9: 1511.

    PubMed  CAS  Google Scholar 

  • Basilico, C., and Moscatelli, D., 1992, The FGF family of growth factors and oncogenes, Adv. Cancer Res. 59: 115.

    Article  PubMed  CAS  Google Scholar 

  • Baskin, P., Doctrow, S., Klagsbrun, M., Svahn, C.M., Folkman, J. and Vlodaysky, I., 1989, Basic fibroblast growth factor binds to subendothelial extracellular matrix and is released by heparitinase and heparin-like molecules, Biochemistry 28: 1737.

    Article  Google Scholar 

  • Bouche, G., Gas, N., Prats, H., Baldin, V., Tauber, J.P., Teissié, J., and Amalric, F., 1987, Basic fibroblast growth factor enters the nucleolus and stimulates the transcription of ribosomal genes in ABAE cells undergoing Go-G1 transition, Proc. Natl. Acad. Sci. U.S.A. 84: 67–70.

    Article  Google Scholar 

  • Breeuwer, M., and Goldfarb, D.S., 1990, Facilitated nuclear transport of histone Hl and other small nucleophilic proteins, Cell 60: 999.

    Article  PubMed  CAS  Google Scholar 

  • Bugler,B., Amalric, F., and Prats, H., 1991, Alternative initiation of translation determines cytoplasmic or nuclear localization of basic fibroblast growth factor, Mol. Cell. Biol. 11: 573.

    Google Scholar 

  • Burgess, W.H., Bizik, J., Mehlman, T., Quarto, N., and Rifkin, D.B., 1991, Direct evidence for methylation of arginine residues in high molecular weight forms of basic fibroblast growth factor, Cell Regul. 2: 87.

    PubMed  CAS  Google Scholar 

  • Chelsky, D., Ralph, R, and Jonak, G., 1989, Sequence requirements for synthetic peptide-mediated translocation to the nucleus, Mol. Cell. Biol. 9: 24–87.

    Google Scholar 

  • Coltrini, D., Rusnati, M., Zoppetti, G., Oreste, P., Iascchi, A., Caccia, P., Bergonzoni, L., and Presta, M., 1993, Biochemical bases of the interaction of human basic fibroblast growth factor with glycosaminoglycans: new insights from trypsin digestion studies, Eur. J. Biochem. in press.

    Google Scholar 

  • Couderc, B., Prats, H., Bayard, F., and Amalric, F., 1991, Potential oncogenic effects of basic fibroblast growth factor requires cooperation between CUG and AUG-initiated forms, Cell Regul. 2: 709.

    PubMed  CAS  Google Scholar 

  • Dell’Era, P., Presta, M., and Ragnotti, G., 1991, Nuclear localization of endogenous basic fibroblast growth factor in cultured endothelial cells, Exp. Cell Res. 192: 505.

    Article  PubMed  Google Scholar 

  • Eppstein, D.A., Marsh, Y.V., Schryver, B.B., and Bertics, P.J., 1989, Inhibition of epidermal growth factor/trasforming growth factor-a stimulated cell growth by a synthetic peptide, J. Cell. Physiol. 141: 420.

    Article  PubMed  CAS  Google Scholar 

  • Eriksson, A.E., Cousens, L.S., Weaver, L.H., Matthews, B.W., 1991, Three-dimensional structure of human basic fibroblast growth factor, Proc. Natl. Acad. Sci. U.S.A. 88: 34–41.

    Article  Google Scholar 

  • Feige, J.J., Bradley, J.D., Fryburg, K., Farris, J., Cousens, L.C., Barr, P.J., and Baird, A., 1989, Differential effects of heparin, fibronectin, and laminin on the phosphorylation of basic fibroblast growth factor by protein kinase C and the catalytic subunit of protein kinase A, J. Cell Biol. 109: 3105.

    Article  PubMed  CAS  Google Scholar 

  • Flaumenhaft, R, Moscatelli, D., Salcsela, O., and Rifkin, D.B., 1989, Role of extracellular matrix in the action of basic fibroblast growth factor: matrix as a source of growth factor for long-term stimulation of plasminogen activator production and DNA synthesis, J. Cell. Physiol. 140: 75.

    Article  PubMed  CAS  Google Scholar 

  • Flaumenhaft, R., Moscatelli, D., and Rifkin, D B, 1990, Heparin and heparan sulphate increase the radius of diffusion and action of basic fibroblast growth factor, J. Cell Biol. 111: 1651.

    Article  PubMed  CAS  Google Scholar 

  • Florkiewicz, R.Z., and Sommer, A., 1989, Human basic fibroblast growth factor gene encodes four polypeptides: three initiate translation from non-AUG codons. Proc. Natl. Acad. Sci. U.S.A. 86: 39–78.

    Article  Google Scholar 

  • Florkiewicz, R.Z., Baird, A., and Gonzalez, A.M., 1991, Multiple forms of bFGF: differential nuclear and cell surface localization, Growth Factors 4: 265.

    Article  PubMed  CAS  Google Scholar 

  • Gospodarowicz, D., Greenburg, G., and Birdwell, RC., 1978, Determination of cellular shape by the extracellular matrix and its correlation with the control of cellular growth, Cancer Res. 38: 41–55.

    Google Scholar 

  • Gospodarowicz, D., and Cheng, J., 1986, Heparin protects basic and acidic FGF from inactivation, J. Cell. Physiol. 128: 475.

    Article  PubMed  CAS  Google Scholar 

  • Gualandris, A., Coltrini, D., Bergonzoni, L., Isacchi, A., Tenca, S., Ginelli, B., and Presta, M., 1993, The N-terminal extension of high molecular weight forms of basic fibroblast growth factor (bFGF) is not essential for the binding of bFGF to nuclear chromatin in transfected NIH 3T3 cells, Growth Factors 8: 49.

    Article  PubMed  CAS  Google Scholar 

  • Habazetti, J., Gondol, D., Wiltscheck, R., Otlewsky, J., Schleicher, M. and Holak, T.A., 1992, Structure of hisactophilin is similar to interleukin-1ß and fibroblast growth factor, Nature 359: 855.

    Article  CAS  Google Scholar 

  • Hageman, G.S., Kirchoff-Rempe, M.A., Lewis, G.P., Fisher, S.K., and Anderson, D.H., 1991, Sequestration of basic fibroblast growth factor in the primate retinal interphotoreceptor matrix, Proc. Natl. Acad. Sci. U.S.A. 88: 6706.

    Article  PubMed  CAS  Google Scholar 

  • Hynes, RO., 1987, Integrins: a family of cell surface receptors, Cell 48: 549.

    Article  PubMed  CAS  Google Scholar 

  • Imamura, T., Englera, K., Zhan, X., Tokita, Y., Forough, R, Roeder, D., Jackson, A., Maier, J.A.M., Hia, T., and Maciag, T., 1990, Science 249: 15–67.

    Article  Google Scholar 

  • Imamura, T., Tokita, Y., and Mitsui, Y.,Recovery of mitogenic activity of a growth factor mutant with a nuclear translocation sequence, 1992, Identification of a heparin-binding growth factor-1 nuclear translocation sequence by deletion mutation analysis, J. Biol. Chem. 267: 56–76.

    Google Scholar 

  • Ingber, D.E., Madri, J.A., and Folkman, J., 1987, Endothelial growth factors and extracellular matrix regulate DNA synthesis through modulation of cell and nuclear expansion, In Vitro Cell. Dev. Biol. 23: 387.

    Article  PubMed  CAS  Google Scholar 

  • Ingber, D.E., and Folkman, J., 1988, Inhibition of angiogenesis through modulation of collagen metabolism, Lab. Invest., 59: 41.

    Google Scholar 

  • Ingber, D.E., and Folkman. J., 1989, Mechanochemical switching between growth and differentiation during fibroblast growth factor-stimulated angiogenesis in vitro: role of extracellular matrix, J. Cell Biol. 109: 317.

    Article  PubMed  CAS  Google Scholar 

  • Ingber, D.E., 1990, Fibronectin controls capillary endothelial cell growth by modulating cell shape, Proc. Natl. Acad. Sci. U.S.A. 87: 35–79.

    Article  Google Scholar 

  • Ingber, D.E., Prusty, D., Frangioni, J.V., Cragoe, E.J.Jr., Lechene, C., and Schwartz, M.A., 1990, Control of intracellular pH and growth by fibronectin in capillary endothelial cells, J. Cell Biol. 110: 1803.

    Article  PubMed  CAS  Google Scholar 

  • Isacchi, A., Statuto, M., Chiesa, R, Bergonzoni, L., Rusnati, M., Sarmientos, P., Ragnotti, G., and Presta, M., 1991, A 6-amino acid deletion in basic fibroblast growth factor dissociates its mitogenic activity from its plasminogen activator-inducing capacity, Proc. Natl. Acad. Sci. U.S.A. 88: 26–28.

    Article  Google Scholar 

  • Johnson, D.E., and Williams, L.T., 1993, Structural and functional diversity in the FGF receptor multigene family, Adv. Cancer Res. 60: 1.

    Article  PubMed  CAS  Google Scholar 

  • Katsuura, M., and Tanaka, S., 1989, Topographic analysis of human epidermal growth factor by monospecific antibodies and synthetic peptides, J. Biochem. 106: 87.

    PubMed  CAS  Google Scholar 

  • Klagsbrun, M., and Baird, A., 1991, A dual receptor system is required for basic fibroblast growth factor activity, Cell 67: 229.

    Article  PubMed  CAS  Google Scholar 

  • Krstenansky, J., Trivedi, D., and Hruby, V.J., 1986, Importance of the 10–13 region of glucagon for its receptor interactions and activation of adenylate cyclase, Biochemistry 25: 3833.

    Article  PubMed  CAS  Google Scholar 

  • Kurokawa, M., Doctrow, S.R., and Klagsbrun, M., 1989, Neutralizing antibodies inhibit the binding of fibroblast growth factor to its receptor but not to heparin, J. Biol. Chem., 264: 76–86.

    Google Scholar 

  • Moscatelli, D., Joseph-Silverstein, J., Presta. M., and Rifkin, D.B., 1988, Multiple forms of an angiogenesis factor: basic fibroblast growth factor, Biochimie 70: 83.

    CAS  Google Scholar 

  • Nestor, J.J., Newman, S R, DeLustro, B., Todaro, G.J., and Schreiber, A.B., 1985, A synthetic fragment of rat transforming growth factor-cc with receptor binding and antigenic properties, Biochem. Biophys. Res. Commun. 129: 226

    Article  PubMed  CAS  Google Scholar 

  • Ornitz, D.M., Yayon, A., Flanagan, J.G., Svahn, C.M., Levi, E., and Leder, P, 1992, Heparin is required for cell-free binding of fibroblast growth factor to a soluble receptor and for mitogenesis in whole cells, Mol. Cell. Biol. 12: 240.

    PubMed  CAS  Google Scholar 

  • Presta, M., Moscatelli, D., Joseph-Silverstein, J., and Rifkin, D.B., 1986, Purification from a human hepatoma cell line of a basic fibroblast growth factor-like molecule that stimulates capillary endothelial cell plasminogen activator production, DNA synthesis, and migration, Mol. Cell. Biol. 6: 40–60.

    Google Scholar 

  • Presta, M., Maier, J.A.M., Rusnati, M., and Ragnotti, G., 1989, Basic fibroblast growth factor is released from endothelial extracellular matrix in a biologically active form, J. Cell. Physiol. 140: 68.

    Article  PubMed  CAS  Google Scholar 

  • Presta, M., Rusnati, M., Urbinati, C., Sommer, A., and Ragnotti, G., 1991, Biologically active synthetic fragments of human basic fibroblast growth factor (bFGF): identification of two asp-gly-argcontaining domains involved in the mitogenic activity of bFGF in endothelial cells, J. Cell. Physiol. 149: 524.

    Article  Google Scholar 

  • Presta, M., Statuto, M., Isacchi, A., Caccia, P., Pozzi, A., Gualandris, A., Rusnati, M., Bergonzoni, L., and Sarmientos, P., 1992, Structure-function relationship of basic fibroblast growth factor: site-directed mutagenesis of a putative heparin-binding and receptor-binding region, Biochem. Biophys. Res. Commun. 185: 1098.

    Article  PubMed  CAS  Google Scholar 

  • Quarto, N., Talarico, D., Florkiewicz, R, and Rifkin, D B, 1991a, Selective expression of high molecular weight basic fibroblast growth factor confers a unique phenotype to NIH 3T3 cells, Cell Regul. 2: 699.

    PubMed  CAS  Google Scholar 

  • Quarto, N., Finger, F.P., and Rifkin, D.B., 1991b, The NH2- terminal extension of high molecular weight bFGF is a nuclear targeting signal, J. Cell. Physiol. 147: 311.

    Article  PubMed  CAS  Google Scholar 

  • Renko, M., Quarto, N., Morimoto, T., and Rifkin, D.B., 1990, Nuclear and cytoplasmic localization of different basic fibroblast growth factor species, J. Cell. Physiol. 144: 108.

    Article  PubMed  CAS  Google Scholar 

  • Ruoslathi, E., and Piershbacher, M.D., 1986, Arg-Gly-Asp: a versatile cell recognition signal, Cell 44: 517.

    Article  Google Scholar 

  • Ruoslathi, E., and Piershbacher, M.D., 1987, New perspectives in cell adhesion: RGD and integrins, Science 238: 493.

    Google Scholar 

  • Schubert, D., Ling, N., and Baird, A., 1987, Multiple influences of a heparin-binding growth factor on neuronal development, J. Cell Biol. 104: 635.

    Article  PubMed  CAS  Google Scholar 

  • Seno, M., Saaada, R, Kurokawa, T., and Igarashi, K., 1990, Carboxyl-terminal structure of basic fibroblast growth factor significantly contributes to its affinity for heparin, Eur. J. Biochem. 188: 239.

    Article  PubMed  CAS  Google Scholar 

  • Silver, P.A., 1991, How proteins enter the nucleus, Cell 64: 489.

    Article  PubMed  CAS  Google Scholar 

  • Sommer, A., and Rifkin, D B, 1989, Interaction of heparin with human basic fibroblast growth factor: protection of the angiogenic protein from proteolytic degradation by a glycosaminoglycan, J. Cell. Physiol. 138: 215.

    Article  PubMed  CAS  Google Scholar 

  • Tessler, S., and Neufeld, G., 1990, Basic fibroblast growth factor accumulates in the nuclei of various bFGF-producing cell types, J. Cell. Physiol. 145: 310.

    Article  PubMed  CAS  Google Scholar 

  • Vlodaysky, J., Folkman J., Sullivan, R, Fridman, R, IshaiMichaeli, R, Sasse, J., and Klagsbrun, M., 1987, Endothelial cell-derived basic fibroblast growth factor: synthesis and deposition into subendothelial extracellular matrix, Proc. Acad Sci. U.S.A. 84: 22–92.

    Google Scholar 

  • Vlodaysky, I., Bar-Shavit, R, Ishai-Michaeli, R, Bashkin, P., and Fuks, Z., 1991, Extracellular sequestration and release of fibroblast growth factor: a regulatory mechanism? Trends Biochem. Sci. 16: 268.

    Article  Google Scholar 

  • Walicke, P.A., Feige J. J., and Baird, A., 1989, Characterization of the neuronal receptor for basic fibroblast growth factor and comparison to receptors on mesenchymal cells, J. Biol. Chem. 264: 4120.

    PubMed  CAS  Google Scholar 

  • Walicke, P.A., and Baird, A., 1991, Internalization and processing of basic fibroblast growth factor by neurons and astrocytes, J. Neurosci. 11: 22–49.

    Google Scholar 

  • Yayon, A., Klagsbrun, M., Esko, J.D., Leder, P., and Ornitz, D.M., 1991, Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor, Cell 64: 841.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, J., Cousens, L.S., Barr, P.J., and Sprang, S.R, 1991, Three-dimensional structure of human basic fibroblast growth factor, a structural homolog to interleukin-113, Proc. Natl. Acad. Sci. U.S.A. 88: 34–46.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Unit of General Pathology and Immunology Department of Biomedical Sciences and Biotechnology School of Medicine, University of Brescia, 25123, Brescia, Italy

    Marco Presta, Marco Rusnati, Anna Gualandris, Patrizia Dell’Era, Chiara Urbinati, Daniela Coltrini, Elena Tanghetti & Mirella Belleri

Authors
  1. Marco Presta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marco Rusnati
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anna Gualandris
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Patrizia Dell’Era
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chiara Urbinati
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Daniela Coltrini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Elena Tanghetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mirella Belleri
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Patras Medical School, Patras, Greece

    Michael E. Maragoudakis

  2. University of Torino Medical School, Torino, Italy

    Pietro M. Gullino

  3. University of Wisconsin Medical School, Milwaukee, Wisconsin, USA

    Peter I. Lelkes

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer Science+Business Media New York

About this chapter

Cite this chapter

Presta, M. et al. (1994). Human Basic Fibroblast Growth Factor: Structure-Function Relationship of an Angiogenic Molecule. In: Maragoudakis, M.E., Gullino, P.M., Lelkes, P.I. (eds) Angiogenesis. NATO ASI Series, vol 263. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9188-4_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-9188-4_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-9190-7

  • Online ISBN: 978-1-4757-9188-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation