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

• Published in: The Journal of cell biology Vol. 111; no. 2; pp. 783 - 792
• Main Authors: Estreicher, Anne, Mühlhauser, Judith, Carpentier, Jean-Louis, Orci, Lelio, Vassalli, Jean-Dominique
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01.08.1990; The Rockefeller University Press
• Subjects: Autoradiography; Biological and medical sciences; Cell Line; Cell lines; Cell Membrane - ultrastructure; Cell membranes; Cell receptors; Cell structures and functions; Cell surface receptors; Cells; Chemotaxis, Leukocyte; Endothelial cells; Enzyme Precursors - genetics; Enzymes; Fundamental and applied biological sciences. Psychology; Humans; In Vitro Techniques; Kinetics; Microscopy, Electron; Miscellaneous; Molecular and cellular biology; Monocytes; Monocytes - physiology; Monocytes - ultrastructure; Plasminogen activators; Plasminogen Activators - genetics; Plasminogen Activators - metabolism; Plasminogen Inactivators - metabolism; proteinase; Receptors; Receptors, Cell Surface - physiology; Receptors, Cell Surface - ultrastructure; Receptors, Urokinase Plasminogen Activator; Urokinase-Type Plasminogen Activator - genetics; Urokinase-Type Plasminogen Activator - metabolism; Human; Radiolabelling; Monocyte; Gel electrophoresis; Enzyme; Enzyme inhibitor; Molecular interaction; Plasminogen activator; Electron microscopy; Cell surface; Proteins; Kinetics; Localization; Biological receptor
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.111.2.783

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.