title: Urokinase-type plasminogen activator/type-2 plasminogen-activator inhibitor complexes are not internalized upon binding to the urokinase-type-plasminogen-activator receptor in THP-1 cells. Interaction of urokinase-type plasminogen activator/type-2 plasminogen-activator inhibitor complexes with the cell surface.
abstract: The urokinase-type plasminogen activator (uPA) and its inhibitor PAI-2 form a covalent complex that, upon binding to the uPA receptor (uPA-R), is cleaved into two fragments of molecular masses 70 kDa and 22 kDa. The 70-kDa fragment results from the interaction of the B chain of uPA and PAI-2 whereas the 22-kDa fragment is the A chain of the enzyme [13]. We prove that, at 37 degrees C, the 70-kDa fragment is released into the medium, whereas the 22-kDa fragment remains bound to the cell surface. uPA complexed with its other specific inhibitor, PAI-1, is cleaved into fragments of identical sizes, but the 70-kDa component is internalized via the alpha 2-macroglobulin receptor. At 4 degrees C, both uPA/PAI-2 complex degradation products remain bound to the uPA-R. We propose that the 70-kDa molecule, which lacks the uPA binding region for uPA-R, is bound to uPA-R via a new binding site, unmasked only when uPA-R is occupied by uPA/PAI-2 complexes.
authors.affiliation: Centro di Endocrinologia ed Oncologia Sperimentale (CEOS), Consiglio Nazionale delle Ricerche, Naples, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Ragno
authors.forename: N
authors.initials: N
authors.lastname: Montuori
authors.forename: G
authors.initials: G
authors.lastname: Rossi
mesh_terms: D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008970:Molecular Weight; D017396:Plasminogen Activator Inhibitor 2 / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D010738:Type C Phospholipases / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: C524898:PLAUR protein, human; D017396:Plasminogen Activator Inhibitor 2; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010738:Type C Phospholipases; D014568:Urokinase-Type Plasminogen Activator