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Activation of human pro-urokinase by unrelated proteases secreted by Pseudomonas aeruginosa.
Beaufort, Nathalie; Seweryn, Paulina; de Bentzmann, Sophie; Tang, Aihua; Kellermann, Josef; Grebenchtchikov, Nicolai; Schmitt, Manfred; Sommerhoff, Christian P; Pidard, Dominique; Magdolen, Viktor.
Afiliação
  • Beaufort N; Department of Obstetrics and Gynecology, Technical University of Munich, Ismaninger Strasse 22, D-81675 Munich, Germany. nbeaufortgbb@yahoo.fr
Biochem J ; 428(3): 473-82, 2010 May 27.
Article em En | MEDLINE | ID: mdl-20337595
Pathogenic bacteria, including Pseudomonas aeruginosa, interact with and engage the host plasminogen (Plg) activation system, which encompasses the urokinase (uPA)-type Plg activator, and is involved in extracellular proteolysis, including matrilysis and fibrinolysis. We hypothesized that secreted bacterial proteases might contribute to the activation of this major extracellular proteolytic system, thereby participating in bacterial dissemination. We report that LasB, a thermolysin-like metalloprotease secreted by Ps. aeruginosa, converts the human uPA zymogen into its active form (kcat=4.9 s-1, Km=8.9 microM). Accordingly, whereas the extracellular secretome from the LasB-expressing pseudomonal strain PAO1 efficiently activates pro-uPA, the secretome from the isogenic LasB-deficient strain PDO240 is markedly less potent in pro-uPA activation. Still, both secretomes induce some metalloprotease-independent activation of the human zymogen. The latter involves a serine protease, which we identified via both recombinant protein expression in Escherichia coli and purification from pseudomonal cultures as protease IV (PIV; kcat=0.73 s-1, Km=6.2 microM). In contrast, neither secretomes nor the pure proteases activate Plg. Along with this, LasB converts Plg into mini-Plg and angiostatin, whereas, as reported previously, it processes the uPA receptor, inactivates the plasminogen activator inhibitor 1, and activates pro-matrix metalloproteinase 2. PIV does not target these factors at all. To conclude, LasB and PIV, although belonging to different protease families and displaying quite different substrate specificities, both activate the urokinase-type precursor of the Plg activation cascade. Direct pro-uPA activation, as also reported for other bacterial proteases, might be a frequent phenomenon that contributes to bacterial virulence.
Assuntos

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Peptídeo Hidrolases / Pseudomonas aeruginosa / Proteínas de Bactérias / Ativador de Plasminogênio Tipo Uroquinase Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Biochem J Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Peptídeo Hidrolases / Pseudomonas aeruginosa / Proteínas de Bactérias / Ativador de Plasminogênio Tipo Uroquinase Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Biochem J Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Alemanha