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Titolo:
Urokinase plasminogen activator induces human smooth muscle cell migrationand proliferation via distinct receptor-dependent and proteolysis-dependent mechanisms
Autore:
Stepanova, V; Mukhina, S; Kohler, E; Resink, TJ; Erne, P; Tkachuk, VA;
Indirizzi:
Cardiolsias Inst, Inst Expt Cardiol, Mol Endocrinol Lab, Moscow 121552, Rus Cardiol Res Inst Moscow Russia 121552 Endocrinol Lab, Moscow 121552, Rus Univel,sel Hosp, Univ Basel Hosp, Dept Res, Cardiovasc Res Lab, CH-4031 Bas Univ Basel Hosp Basel Switzerland CH-4031 ardiovasc Res Lab, CH-4031 Bas Kantonsspital Luzern, CH Luzern, Div Cardiol, Luzern, Switzerland Kantonsspital Luzern Luzern Switzerland iv Cardiol, Luzern, Switzerland
Titolo Testata:
MOLECULAR AND CELLULAR BIOCHEMISTRY
fascicolo: 1-2, volume: 195, anno: 1999,
pagine: 199 - 206
SICI:
0300-8177(199905)195:1-2<199:UPAIHS>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT CAROTID-ARTERY; GROWTH-FACTOR; SIGNAL-TRANSDUCTION; ENDOTHELIAL-CELLS; HUMAN FIBROBLASTS; CHEMOTAXIS; INDUCTION; BINDING; EXPRESSION; CLEAVAGE;
Keywords:
urokinase; isoforms; human smooth muscle cell; migration; proliferation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Tkachuk, VA Cardiolsias Inst, Inst Expt Cardiol, Mol Endocrinol Lab, Moscow 121552, Rus Cardiol Res Inst Moscow Russia 121552 ab, Moscow 121552, Rus
Citazione:
V. Stepanova et al., "Urokinase plasminogen activator induces human smooth muscle cell migrationand proliferation via distinct receptor-dependent and proteolysis-dependent mechanisms", MOL C BIOCH, 195(1-2), 1999, pp. 199-206

Abstract

In order to define the relative contribution of the proteolytic domain andthe receptor-binding domain of urokinase plasminogen activator (uPA) toward its mitogenic properties we studied the effects of different uPA isoformson migration and proliferation of human aortic smooth muscle cells (hSMC). The isoforms tested included native human glycosylated uPA, and two recombinant uPA forms, namely a recombinant uPA with wild type structure (r-uPA),and a uPA-mutant in which the first 24 N-terminal amino acid residues of the receptor binding domain were replaced by 13 foreign amino acid residues (r-uPAmut). Cell migration was evaluated using a micro-Boyden chamber assay, and cell proliferation assessed by measurement of [H-3]-thymidine incorporation into DNA. Competition binding studies on hSMC using I-125-r-uPA as ligand demonstrated that r-uPA and r-uPAmut exhibited equivalent displacement profiles. However, migration of hSMC was promoted by r-uPA and not by r-uPAmut. r-uPA-induced migration occurred at concentrations (half-maximally effective concentration of 2 nM) approximating the Kd for uPA-uPAR binding (1 nM). r-uPA-induced migration was not affected by the plasmin inhibitor aprotinin. In contrast to their differential chemotactic properties, uPA, r-uPA and r-uPAmut, which possess similar proteolytic activities, all stimulated [H-3]-thymidine incorporation in hSMC. Since the [H-3]-thymidine incorporation response to each isoform occurred at concentrations (> 50 nM) much higher than necessary for uPAR saturation by ligand (1 nM), this mitogenic response may be independent of binding to uPAR. [H-3]-thymidine incorporation responses to r-uPA and -uPAmut were sensitive to the plasmin inhibitor aprotinin, and uPA stimulated DNA synthesis was inhibited by plasminogen activator inhibitor. We conclude that hSMC migration in response to uPA dependsupon on its binding to uPAR, whereas uPA-stimulated DNA synthesis in thesecells requires proteolysis and plasmin generation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/10/20 alle ore 00:16:53