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

PRESTA, Marco;RUSNATI, Marco;
1992-01-01
1992
MIUR (compresi PRIN FIRB,FISR)
LS3_7 Cell signalling and cellular interactions
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
sì
2-s2.0-0026777022
WOS:A1992JB54100043
Esperti anonimi
Inglese
Internazionale
185
3
1098
1107
9
1378264
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.
Amino Acid Sequence; Animals; Base Sequence; Binding Sites; Binding; Competitive; Cattle; Cell Division; Cell Line; Transformed; Cell Membrane; Chemotaxis; Cloning; Molecular; Endothelium; Vascular; Enzyme Induction; Fibroblast Growth Factor 2; Heparin; Humans; Kinetics; Molecular Sequence Data; Mutagenesis; Site-Directed; Neovascularization; Pathologic; Oligodeoxyribonucleotides; Plasmids; Plasminogen Activators; Receptors; Cell Surface; Fibroblast Growth Factor
Ateneo di appartenenza
9
info:eu-repo/semantics/article
262
Presta, Marco; M., Statuto; A., Isacchi; P., Caccia; A., Pozzi; A., Gualandris; Rusnati, Marco; L., Bergonzoni; P., Sarmientos
1 Contributo su Rivista::1.1 Articolo in rivista
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1.1 Articolo in rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11379/31118
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