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Istituto di scienza dell'alimentazione

Torna all'elenco Contributi in rivista anno 2003

Contributo in rivista

Tipo: Articolo in rivista

Titolo: Identification of a novel domain of fibroblast growth factor- 2 controlling its angiogenic properties.

Anno di pubblicazione: 2003

Autori: Facchiano A, Russo K, Facchiano AM, De Marchis F, Facchiano F, Ribatti D, Aguzzi MS, Capogrossi MC

Affiliazioni autori: Facchiano A, Russo K, De Marchis F, Facchiano F, Aguzzi MS, Capogrossi MC: Laboratorio Patologia Vascolare, Istituto Dermopatico dell'Immacolata, IRCCS, 00167 Roma, Italy Facchiano AM: Istituto di Scienze dell'Alimentazione, CNR, Avellino Ribatti D: Dipartimento Anatomia Umana e Istologia, UniversitÓ degli Studi di Bari, 70124 Bari, Italy

Autori CNR:

  • ANGELO FACCHIANO

Abstract: Fibroblast growth factor 2 (FGF-2) is a potent factor modulating the activity of many cell types. Its dimerization and binding to high affinity receptors are considered to be necessary steps to induce FGF receptor phosphorylation and signaling activation. A structural analysis was carried out and a region encompassing residues 48-58 of human FGF-2 was identified, as potentially involved in FGF-2 dimerization. A peptide (FREG-48-58) derived from this region strongly and specifically inhibited FGF-2 induced proliferation and migration of primary bovine aorta endothelial cells (BAEC) in vitro, and markedly reduced FGF-2-dependent angiogenesis in two distinct in vivo assays. To further investigate the role of region 48-58, a polyclonal antibody raised against FREG-(48-58) was tested and was found to block FGF-2 action in vitro. Human FGF-2 has three histidine residues, one falling within the region 48-58. Chemical modification of histidine residues blocked FGF-2 activity and FREG-(48-58) inhibitory effect in vitro, indicating that histidine residues, in particular the one within FREG-(48-58) region, play a crucial role in the observed activity. Additional experiments showed that FREG-(48-58) specifically interacted with FGF-2, impaired FGF-2-interaction with itself, with heparin and with FGF receptor 1, and inhibited FGF-2-induced receptor phosphorylation and FGF-2 internalization. These data indicate for the first time that region 48-58 of FGF-2 is a functional domain controlling FGF-2 activity.

Pagine da: 8751

Pagine a: 8760

Numero volume: 278

Parole chiave:

  • Fibroblast growth factor 2
  • peptide attivo
  • molecular modelling
  • molecular docking

Altre informazioni: 15

Strutture CNR:

 
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