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

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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°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 a2‐macroglobulin receptor. At 4°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.

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