Human single-chain urokinase is activated by the omptins PgtE of Salmonella enterica and Pla of Yersinia pestis despite mutations of active site residues

Autor: Hanna M, Järvinen, Liisa, Laakkonen, Johanna, Haiko, Tiira, Johansson, Katri, Juuti, Marjo, Suomalainen, Carmen, Buchrieser, Nisse, Kalkkinen, Timo K, Korhonen
Přispěvatelé: University of Helsinki, Department of Bacteriology and Immunology [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Biologie des bactéries intracellulaires, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), HiLIFE - Institute of Biotechnology [Helsinki] (BI), Helsinki Institute of Life Science (HiLIFE), This work received financial support from the University of Helsinki, the Academy of Finland (ERA-NET Pathogenomics grant number 1130202), the Institut Pasteur, the Centre National de la Recherche Scientifique (CNRS), and the Institut Carnot-Pasteur MI., European Project: Pathomics, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Molecular Microbiology
Molecular Microbiology, Wiley, 2013, 89 (3), pp.507-517. ⟨10.1111/mmi.12293⟩
Molecular Microbiology, 2013, 89 (3), pp.507-517. ⟨10.1111/mmi.12293⟩
ISSN: 0950-382X
1365-2958
Popis: International audience; Fibrinolysis is important in cell migration and tightly regulated by specific inhibitors and activators; of the latter, urokinase (uPA) associates with enhancement of cell migration. Active uPA is formed through cleavage of the single-chain uPA (scuPA). The Salmonella enterica strain 14028R cleaved human scuPA at the peptide bond Lys158-Ile159, the site cleaved also by the physiological activator human plasmin. The cleavage led to activation of scuPA, while no cleavage or activation were detected with the mutant strain 14028R lacking the omptin protease PgtE. Complementation and expression studies confirmed the role of PgtE in scuPA activation. Similar cleavage and activation of scuPA were detected with recombinant Escherichia coli expressing the omptin genes pla from Yersinia pestis, ompT and ompP from E. coli, sopA from Shigella flexneri, and leo from Legionella pneumophila. For these omptins the activation of scuPA is the only shared function so far detected. Only poor cleavage and activation of scuPA were seen with YcoA of Y. pestis and YcoB of Yersinia pseudotuberculosis that are considered to be proteolytically inactive omptin variants. Point mutations of active site residues in Pla and PgtE had different effects on the proteolysis of plasminogen and of scuPA, indicating versatility in omptin proteolysis. © 2013 John Wiley & Sons Ltd.
Databáze: OpenAIRE
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