Activation of pro-urokinase by the human T cell-associated serine proteinase HuTSP-1.
The human T cell-associated serine proteinase-1 (HuTSP-1) is expressed by activated T lymphocytes and is exocytosed upon their interaction with target cells. Here, we report that HuTSP-1 is able to convert single-chain human pro-urokinase into the active two-chain enzyme. Time-dependent activation by HuTSP-1 of recombinant human pro-urokinase as well as natural pro-urokinase derived from human melanoma cells was demonstrated in a chromogenic assay specific for active urokinase type plasminogen activator and in immunoblotting experiments revealing the conversion of single-chain into two-chain urokinase. Control experiments excluded plasmin as the activating agent. These data suggest a novel pathway for plasmin generation during T cell-mediated processes such as immune responses and extravasation of immune cells.
Brunner
G
G
German Cancer Research Centre, Institute of Immunology and Genetics, Heidelberg, FRG.
Simon
M M
MM
Kramer
M D
MD
D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D005341:Fibrinolysin / Q000032:analysis; D015971:Gene Expression Regulation, Enzymologic; D053804:Granzymes; D006801:Humans; D006868:Hydrolysis; D015151:Immunoblotting; D008545:Melanoma / Q000378:metabolism; D010960:Plasminogen Activators / Q000032:analysis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000378:metabolism*
D011994:Recombinant Proteins; D053804:Granzymes; D010960:Plasminogen Activators; D012697:Serine Endopeptidases; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator; C509212:GZMA protein, human