| Inhibition of receptor-bound urokinase by plasminogen-activator inhibitors. | |
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MedLine Citation:
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PMID: 2161846 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Urokinase-type plasminogen activator (uPA) binds to a specific receptor on various cell types, the bound molecule retaining its enzymatic activity against plasminogen. We have now investigated whether receptor-bound uPA also retains the ability to react with and be inhibited by plasminogen activator inhibitors (PAI-1 and PAI-2). uPA bound to its receptor on human U937 monocyte-like cells was inhibited by PAI-1 (in its active form in the presence of vitronectin fragments) with an association rate constant of 4.5 x 10(6) M-1 s-1, which was 40% lower than that obtained for uPA in solution (7.9 x 10(6) M-1 s-1). The inhibition of uPA by PAI-2 was decreased to a similar extent by receptor binding, falling from 5.3 x 10(5) to 3.3 x 10(5) M-1 s-1. Stimulation of U937 cells with phorbol 12-myristate 13-acetate was accompanied by a further reduction in receptor-bound uPA inhibition by PAI-1 and PAI-2 to 1.7 x 10(6) and 1.1 x 10(5) M-1 s-1, respectively. These constants although lower than those for uPA in solution still represent rather rapid inhibition of the enzyme, and demonstrate that uPA bound to its specific cellular receptor remains available for efficient inhibition by PAI's, which may therefore play a major role in controlling cell-surface plasminogen activation and extracellular proteolytic activity. |
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Authors:
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V Ellis; T C Wun; N Behrendt; E Rønne; K Danø |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 265 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 1990 Jun |
Date Detail:
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Created Date: 1990-07-16 Completed Date: 1990-07-16 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 9904-8 Citation Subset: IM |
Affiliation:
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Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antibodies Antigen-Antibody Complex Cell Line Enzyme Precursors / metabolism* Humans Kinetics Plasminogen / metabolism Plasminogen Activators / metabolism* Plasminogen Inactivators / pharmacology* Receptors, Cell Surface / drug effects, metabolism* Receptors, Urokinase Plasminogen Activator Tetradecanoylphorbol Acetate / pharmacology Tumor Cells, Cultured / metabolism Urokinase-Type Plasminogen Activator / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Antibodies; 0/Antigen-Antibody Complex; 0/Enzyme Precursors; 0/PLAUR protein, human; 0/Plasminogen Inactivators; 0/Receptors, Cell Surface; 0/Receptors, Urokinase Plasminogen Activator; 16561-29-8/Tetradecanoylphorbol Acetate; 9001-91-6/Plasminogen; EC 3.4.21.-/Plasminogen Activators; EC 3.4.21.73/Urokinase-Type Plasminogen Activator |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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