Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Role of endothelial cell extracellular signal-regulated kinase(1/2) in urokinase-type plasminogen activator upregulation and in vitro angiogenesis byfibroblast growth factor-2
Autore:
Giuliani, R; Bastaki, M; Coltrini, D; Presta, M;
Indirizzi:
Univ Brescia, Dept Biomed Sci & Biotechnol, Unit Gen Pathol & Immunol, I-25123 Brescia, Italy Univ Brescia Brescia Italy I-25123 hol & Immunol, I-25123 Brescia, Italy
Titolo Testata:
JOURNAL OF CELL SCIENCE
fascicolo: 15, volume: 112, anno: 1999,
pagine: 2597 - 2606
SICI:
0021-9533(199908)112:15<2597:ROECES>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
NUCLEAR TRANSLOCATION SEQUENCE; SITE-DIRECTED MUTAGENESIS; PROTEIN-KINASE; RECEPTOR-BINDING; BIOLOGICAL-ACTIVITY; MITOGENIC ACTIVITY; HEPARIN-BINDING; 3-DIMENSIONAL STRUCTURE; FACTOR MUTANT; IN-VITRO;
Keywords:
angiogenesis; endothelium; ERK; FGF; signaling; urokinase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Presta, M Univ Brescia, Dept Biomed Sci & Biotechnol, Unit Gen Pathol & Immunol, I-25123 Brescia, Italy Univ Brescia Brescia Italy I-25123 nol, I-25123 Brescia, Italy
Citazione:
R. Giuliani et al., "Role of endothelial cell extracellular signal-regulated kinase(1/2) in urokinase-type plasminogen activator upregulation and in vitro angiogenesis byfibroblast growth factor-2", J CELL SCI, 112(15), 1999, pp. 2597-2606

Abstract

Downstream signaling triggered by the binding of fibroblast growth factor-2 (FGF2) to its tyrosine-kinase receptors involves the activation of mitogen-activated protein kinase kinase (MEK) with consequent phosphorylation of extracellular signal-regulated kinases (ERKs), Here we demonstrate that FGF2 induces ERK1/2 activation in bovine aortic endothelial (BAE) cells and that the continuous presence of the growth factor is required for sustained ERK1/2 phosphorylation, This is prevented by the MEK inhibitors PD 098059 and U0126, which also inhibit FGF(2)-mediated upregulation of urokinase-type plasminogen activator (uPA) and in vitro formation of capillary-like structures in three-dimensional type I collagen gel,Various FGF2 mutants originated by deletion or substitution of basic aminoacid residues in the amino terminus or in the carboxyl terminus of FGF2 retained the capacity to induce a long-lasting activation of ERK1/2 in BAE cells, Among them, K(128)Q/R(129)Q-FGF2 was also able to stimulate uPA production and morphogenesis whereas R(129)Q/K(134)Q-FGF2 caused uPA upregulationonly In contrast, K(27,30)Q/R(31)Q-FGF2, K(128)Q/K(138)Q-FGF2 and R(115,129)QM(119,128)Q-FGF2 exerted a significant uPA-inducing and morphogenic activity in an ERK1/2-dependent manner only in the presence of heparin, Furthermore, no uPA upregulation and morphogenesis was observed in BAE cells treated with the deletion mutant Delta(27-32)-FGF2 even in the presence of soluble heparin, Thus, mutational analysis of FGF2 dissociates the capacity of the growth factor to induce a persistent activation of ERK1/2 from its ability to stimulate uPA upregulation and/or in vitro angiogenesis. In conclusion, the data indicate that ERK1/2 phosphorylation is a key stepin the signal transduction pathway switched on by FGF2 in endothelial cells, Nevertheless, a sustained ERK1/2 activation is not sufficient to triggeruPA upregulation and morphogenesis. FGF2 mutants may represent useful tools to dissect the signal transduction pathway(s) mediating the complex response elicited by an angiogenic stimulus in endothelial cells.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 15:40:16