Single-chain urokinase-type plasminogen activator bound to its receptor is relatively resistant to plasminogen activator inhibitor type 1. 1996

A A Higazi, and A Mazar, and J Wang, and R Reilly, and J Henkin, and D Kniss, and D Cines
Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia 19104, USA.

Urokinase-type plasminogen activator (uPA) is synthesized as single-chain protein (scuPA) with little intrinsic activity. scuPA is activated when it is converted to two-chain urokinase (tcuPA) by plasmin or when it binds as a single-chain molecule to its cellular receptor (uPAR). Previous data indicate that complexes between scuPA and its receptor have somewhat higher affinity for plasminogen than does tcuPA. The current study indicates that plasminogen activator activity of scuPA bound to recombinant, soluble uPAR (suPAR) is also fivefold less sensitive to inhibition by plasminogen activator type 1 (PAI-1) than is soluble or receptor-bound tcuPA. Binding of PaI-1 to suPAR/scuPA complexes is totally reversible and can be overcome by increasing the concentration of plasminogen, suggesting a competitive mechanism of inhibition (Ki = 18 nmol/L). Binding of scuPA to suPAR also retards its cleavage by plasmin. These results indicates that binding of single-chain urokinase to its receptor promotes its activity, retards its inhibition, and protects it from conversion to a two-chain form of the enzyme, a step that may precede its inactivation and clearance from cell surfaces. These results are consistent with a physiologic role for receptor-bound single-chain urokinase as a cellular plasminogen activator.

UI MeSH Term Description Entries
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014568 Urokinase-Type Plasminogen Activator A proteolytic enzyme that converts PLASMINOGEN to FIBRINOLYSIN where the preferential cleavage is between ARGININE and VALINE. It was isolated originally from human URINE, but is found in most tissues of most VERTEBRATES. Plasminogen Activator, Urokinase-Type,U-Plasminogen Activator,Urinary Plasminogen Activator,Urokinase,Abbokinase,Kidney Plasminogen Activator,Renokinase,Single-Chain Urokinase-Type Plasminogen Activator,U-PA,Single Chain Urokinase Type Plasminogen Activator,U Plasminogen Activator,Urokinase Type Plasminogen Activator
D017395 Plasminogen Activator Inhibitor 1 A member of the serpin family of proteins. It inhibits both the tissue-type and urokinase-type plasminogen activators. PAI-1,SERPINE1 Protein,Serpin E1,Type 1 Plasminogen Activator Inhibitor,E1, Serpin,Protein, SERPINE1
D055293 Receptors, Urokinase Plasminogen Activator An extracellular receptor specific for UROKINASE-TYPE PLASMINOGEN ACTIVATOR. It is attached to the cell membrane via a GLYCOSYLPHOSPHATIDYLINOSITOL LINKAGE and plays a role in the co-localization of urokinase-type plasminogen activator with PLASMINOGEN. Antigens, CD87,Urokinase Plasminogen Activator Receptor,Urokinase Type Plasminogen Activator Receptor,Urokinase-Type Plasminogen Activator Receptor,CD87 Antigen,Plasminogen Activator Receptor, Urokinase Type,Plasminogen Activator, Urokinase Receptor,Plasminogen Activator, Urokinase Receptors,Receptor, Pro-Urokinase,Receptor, Urokinase Plasminogen Activator,U-PA Receptor,Upar Receptor,Urokinase Plasminogen Activator Receptors,Urokinase-Type Plasminogen Activator Receptors,Antigen, CD87,CD87 Antigens,Pro-Urokinase Receptor,Receptor, Pro Urokinase,Receptor, U-PA,Receptor, Upar,U PA Receptor,Urokinase Type Plasminogen Activator Receptors

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