Structure-function relationship of basic fibroblast growth factor: Site-directed mutagenesis of a putative heparin-binding and receptor-binding region

M. Presta, M. Statuto, A. Isacchi, P. Caccia, A. Pozzi, A. Gualandris, M. Rusnati, L. Bergonzoni, P. Sarmientos

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Basic residues Arg-118, Lys-119, Lys-128, and Arg-129 within a putative heparin-binding and receptor-binding region of the 155-amino acid form of basic fibroblast growth factor (bFGF) have been changed to neutral glutamine residues by site-directed mutagenesis of the human bFGF cDNA. The bFGF mutant (M6B-bFGF) was expressed in E. coli and purified to homogeneity. When compared to wild type bFGF, M6B-bFGF showed in cultured endothelial cells a similar receptor-binding capacity and mitogenic activity, but a reduced affinity for heparin-like low affinity binding sites, a reduced chemotactic activity, and a reduced capacity to induce the production of urokinase-type plasminogen activator. In vivo, M6B-bFGF lacked a significant angiogenic activity. Modifications of both the primary and the tertiary structure of bFGF appear to be responsible for the modified biological properties of M6B-bFGF, thus confirming the possibility to dissociate at the structural level some of the biological activities exerted by bFGF on endothelial cells.

Original languageEnglish
Pages (from-to)1098-1107
Number of pages10
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - Jun 30 1992


ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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