Processing of complex between urokinase and its type-2 inhibitor on the cell surface. A possible regulatory mechanism of urokinase activity.
Complexes between the urokinase-type plasminogen activator (uPA) and its type-2 inhibitor (PAI-2) are bound by a cell-surface receptor for uPA and rapidly cleaved into two fragments of 70 and 22 kDa. The 70-kDa fragment contains the active site of uPA and PAI-2, while the 22-kDa species was identified as the amino terminal fragment of uPA, that binds specifically to the receptor. When the experiment is performed at 4 degrees C, both fragments remain bound to the cell surface and can be eluted by acid treatment. We therefore postulate that after the binding of the uPA-PAI-2 complex, a new binding site for the 70-kDa species becomes available. This additional binding favours the cleavage of the complex into the 70-and 22-kDa fragments; the 70-kDa species is endocytosed or released, while the 22-kDa fragment remains on the cell surface to prevent the binding of intact uPA.
Centro di Endocrinologia ed Oncologia Sperimentale (CEOS), Consiglio Nazionale delle Ricerche, Naples, Italy.
P
P
Ragno
N
N
Montuori
J D
JD
Vassalli
G
G
Rossi
D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006706:Homeostasis; D006801:Humans; D008970:Molecular Weight; D017396:Plasminogen Activator Inhibitor 2 / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000302:isolation & purification / Q000378:metabolism*
C524898:PLAUR protein, human; D017396:Plasminogen Activator Inhibitor 2; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator