PMID:23763588

Citation	Järvinen, HM, Laakkonen, L, Haiko, J, Johansson, T, Juuti, K, Suomalainen, M, Buchrieser, C, Kalkkinen, N and Korhonen, TK (2013) Human single-chain urokinase is activated by the omptins PgtE of Salmonella enterica and Pla of Yersinia pestis despite mutations of active site residues. Mol. Microbiol. 89:507-17
Abstract	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.
Links	PubMed Online version:10.1111/mmi.12293
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
SULAA:C1DVR5		GO:0030377: U-plasminogen activator receptor activity	ECO:0000315:		F		Fig 3/4 - show that scuPA is a common substrate for omptin proteases	complete CACAO 8770
SULAA:C1DVR5		GO:0008233: peptidase activity	ECO:0000315:		F		Fig 2 shows that PgtE activates scuPA	complete CACAO 8771

References

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