Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Soluble highly active conjugates were obtained after complex formation or covalent binding of trypsin and urokinase with polymers of various chemical structure as well as by means of condensation of the enzyme molecules as a result of which oligo- and heterooligoproteins were produced. Pharmacological activity of the conjugates obtained was studied in the course of treatment of rabbits with experimental hyphemia. All the preparations produced exhibited high therapeutic efficiency: the time of hyphemia resorption was decreased, the effect of immobilized enzymes was prolonged as compared with controls. Dependence on the molecular mass and the dose of enzymatic preparations of the period of hyphemia resorption was studied using heteromers of urokinase and hemoglobin. Maximal activity was noted with the preparations of molecular mass 4.10(5) daltons; they maintained the optimal level of pharmacological activity even after 4-fold decrease in the dose used as compared with other immobilized preparations of trypsin and urokinase. The immobilized preparations were 20-fold more effective as compared with native unmodified enzymes.
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PMID:[Immobilized thrombolytic enzymes and their use in ophthalmology]. 404 87

Ovarian cancer metastasis is associated with an increase in the urokinase-type plasminogen activator (uPA) and its receptor uPAR. We present evidence that binding of uPA to uPAR provokes a mitogenic response in the human ovarian cancer cell line OV-MZ-6 in which endogenous uPA production had been significantly reduced by stable uPA 'antisense' transfection. High molecular weight (HMW) uPA, independent of its enzymatic activity, produced an up to 95% increase in cell number concomitant with 2-fold elevated [3H]thymidine incorporation as did the catalytically inactive but uPAR binding amino-terminal fragment of uPA, ATF. uPA-induced cell proliferation was significantly decreased by blocking uPA/uPAR interaction by the monoclonal antibody IIIF10 and by soluble uPAR. The efficiency of the uPAR binding synthetic peptide cyclo19,31 uPA19-31 to enhance OV-MZ-6 cell growth proved this molecular domain to be the minimal structural determinant for uPA mitogenic activity. Dependence of uPA-provoked cell proliferation on uPAR was further demonstrated in Raji cells which do not express uPAR and were thus not induced by uPA. However, upon transfection with full-length uPAR, Raji cells acquired a significant growth response to HMW uPA and ATF.
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PMID:Urokinase induces proliferation of human ovarian cancer cells: characterization of structural elements required for growth factor function. 982 67

Improvements in preparations of tissue activator and plasminogen and termination of activation by epsilon aminocaproic acid have permitted the use of a quantitative caseinolytic assay for the measurement of the plasmin formed. The following data indicate that the activation of plasminogen by tissue activator is catalytic: a) Biphasic curve obtained when velocity was plotted against plasminogen concentration. b) First order kinetics. c) Dependence of the turnover number on tissue activator concentration. The temperature and pH stability of tissue activator were similar to those reported for urokinase. Since both of these enzymes have now been shown to activate plasminogen by a catalytic mechanism, these data support the suggestion that urokinase may be an excretory form of tissue activator which has been released into the circulation.
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PMID:Mechanism of action and some properties of a tissue activator of plasminogen. 1695 70