Aerolysin is a secreted bacterial toxin that perforates the plasma membrane of a target cell with lethal consequences. Previously explored native and epitope-tagged forms of the toxin do not allow site-specific modification of the mature toxin with a probe of choice. We explore sortase-mediated transpeptidation reactions (sortagging) to install fluorophores and biotin at three distinct sites in...

Urokinase-type plasminogen activator (uPA) binds to its receptor (uPAR) with a K(d) of about 1 nm. The catalytic activity of the complex is apparent at uPA concentrations close to K(d). Other functions of the complex, such as signal transduction, are apparent at much higher concentrations (35-60 nm). In the present study, we show that uPA and recombinant soluble uPAR (suPAR), at concentrations ...

Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play an important role in cell guidance and chemotaxis during normal and pathological events. uPAR is GPI-anchored and the mechanism by which it transmits intracellular polarity cues across the plasma membrane during directional sensing has not been elucidated. The constitutively recycling endocytic receptor Endo180 forms a trim...

We report the crystal structure of a soluble form of human urokinase-type plasminogen activator receptor (uPAR/CD87), which is expressed at the invasive areas of the tumor-stromal microenvironment in many human cancers. The structure was solved at 2.7 A in association with a competitive peptide inhibitor of the urokinase-type plasminogen activator (uPA)-uPAR interaction. uPAR is composed of thr...

Urokinase-type plasminogen activator (u-PA) is known to be secreted by malignant cells during proliferation and migration, and is associated with tumour cell invasion and metastasis. This study was undertaken to evaluate whether u-PA is significantly increased in carcinomatous pleural fluids compared to those due to other aetiologies, and to identify the cells in the pleural space that are invo...

AIMS To investigate the fibrinolytic activity of normal and calculous human bile. METHODS Fibrinolytic properties of the biliary tract were studied in patients with gall bladder stones (n = 7) compared with acalculous gall bladders (n = 8). RESULTS Bile plasminogen activating activity was detected in a wide range in both groups (calculous bile median 0.35 IU/ml; range: 0.06-6.59, versus nor...

Tissue-type plasminogen activator (t-PA), purified from the culture fluid of a stable human melanoma cell line, is a serine protease, different from urokinase, with a molecular weight of about 70,000. It is composed of one polypeptide chain, which is converted to a two-chain molecule by limited plasmic action. Activation of plasminogen to plasmin occurs by cleavage of the Arg 560-Val 561 peptid...

T HROMBOTIC COMPLICATIONS of cardiovascular disease are a main cause of death and disability and, consequently, thrombolysis could favorably influence the outcome of such life-threatening diseases as myocardial infarction, cerebrovascular thrombosis, and venous thromboembolism. Thrombolytic agents are plasminogen activators that convert plasminogen, the inactive proenzyme of the fibrinolytic sy...

Urokinase-related proteins in human urine occur mainly as a 1: 1 complex of urokinase with an inhibitor (Stump, D. C., Thienpont, M., and Collen, D. (1986) J. Biol. Chem. 261, 1267-1273). BALB/c mice were immunized with this urokinase-urokinase inhibitor complex and spleen cells fused with mouse myeloma cells, resulting in hybridomas producing monoclonal antibodies. Three antibodies reacting wi...