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

نویسندگان

  • A Estreicher
  • J Mühlhauser
  • J L Carpentier
  • L Orci
  • J D Vassalli
چکیده

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.

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عنوان ژورنال:
  • The Journal of Cell Biology

دوره 111  شماره 

صفحات  -

تاریخ انتشار 1990