The receptor for urokinase type plasminogen activator polarizes expression of the protease to the leading edge of migrating monocytes and promotes degradation of enzyme inhibitor complexes.
Receptor-bound urokinase-type plasminogen activator (uPA) remains associated to the surface of human monocytes for many hours. Monocytes induced to migrate in a chemotactic gradient of f-Met-Leu-Phe rapidly polarize their uPA receptors to the leading front of the cells. Receptor-bound enzyme can be inhibited by plasminogen activator inhibitor 2 (PAI-2), with a kinetics comparable to that determined for the free enzyme, and uPA/PAI-2 complexes can bind to the uPA receptor. In contrast to the active enzyme, the uPA/PAI-2 complex is rapidly cleared from the monocyte cell surface; this involves an initial cleavage of the complex at the cell surface, followed by endocytosis and degradation. These results indicate that the uPA receptor can function both to focus plasmin-mediated extracellular matrix degradation in front of migrating cells, and to target uPA/PAI-2 enzyme/inhibitor complexes for degradation; they suggest that this receptor is a key determinant in the control of uPA-catalyzed extracellular proteolysis.
Estreicher
A
A
Institute of Histology and Embryology, University of Geneva Medical School, Switzerland.
Mühlhauser
J
J
Carpentier
J L
JL
Orci
L
L
Vassalli
J D
JD
D002460:Cell Line; D002462:Cell Membrane / Q000648:ultrastructure; D002634:Chemotaxis, Leukocyte; D004792:Enzyme Precursors / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008854:Microscopy, Electron; D009000:Monocytes / Q000502:physiology* / Q000648:ultrastructure; D010960:Plasminogen Activators / Q000235:genetics* / Q000378:metabolism; D015849:Plasminogen Inactivators / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology* / Q000648:ultrastructure; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics* / Q000378:metabolism
D004792:Enzyme Precursors; C524898:PLAUR protein, human; D015849:Plasminogen Inactivators; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator