title: Functional characteristics of receptor-bound urokinase on human monocytes: catalytic efficiency and susceptibility to inactivation by plasminogen activator inhibitors.
abstract: We compared urokinase-type plasminogen activator (u-PA) in fluid phase and u-PA bound with its receptor on human blood monocytes with respect to proteolytic activity and susceptibility to inactivation by the plasminogen activator inhibitors PAI-1 and PAI-2. Receptor-bound u-PA is catalytically twice as efficient as fluid-phase u-PA. Fluid-phase u-PA is susceptible to rapid inhibition by PAI-1 and PAI-2 at an estimated PAI:u-PA molar ratio of 2:1. In contrast, u-PA bound to endogenously occupied receptors is inhibited by PAI-2 only at PAI:u-PA molar ratios of 20:1, but is not inhibited by PAI-1, u-PA/PAI-1 and u-PA/PAI-2 complexes bind to the receptor with a tenfold lower affinity than u-PA itself. Thus, competition of u-PA/PAI complexes with fluid-phase u-PA for binding to the receptor is unlikely to affect the overall plasminogen activator activity of the monocyte. These findings demonstrate that the activity of receptor-bound u-PA can be modulated by PAI-2, but not by PAI-1, to adjust the cell's proteolytic activity to different local situations.
authors.affiliation: Department of Rheumatology/Immunology, Brigham and Women's Hospital, Boston, MA 02115.
authors.forename: J C
authors.initials: JC
authors.lastname: Kirchheimer
authors.forename: H G
authors.initials: HG
authors.lastname: Remold
mesh_terms: D002384:Catalysis; D004789:Enzyme Activation / Q000187:drug effects; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D015849:Plasminogen Inactivators; D011956:Receptors, Cell Surface / Q000032:analysis / Q000187:drug effects / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D012995:Solubility; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology
chemical_list: D006023:Glycoproteins; C524898:PLAUR protein, human; D015849:Plasminogen Inactivators; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator