Urokinase/urokinase receptor system: internalization/degradation of urokinase-serpin complexes: mechanism and regulation

Biol Chem Hoppe Seyler. 1995 Mar;376(3):143-55.


The urokinase-type plasminogen activator (uPA) is secreted as a single-chain inactive zymogen (pro-uPA). Upon its secretion, pro-uPA binds to its glycosylphosphatidylinositol-anchored specific cell receptor (uPAR). The activation of pro-uPA to the active two-chain uPA is accelerated with uPAR-bound pro-uPA and is achieved by plasmin and proteases of other classes like cathepsins G and L. uPAR-bound uPA is susceptible to inhibition by its specific inhibitors (PAI-1, PAI-2, and PN-1). uPA-PAI-1 and uPA-PN-1 complexes, but not free uPA, are readily internalized and degraded through a mechanism that involves the multiligand receptors alpha 2-macroglobulin receptor/low density lipoprotein receptor-associated protein (alpha 2-MR) and epithelial glycoprotein 330 (gp330). Upon uPA-inhibitor internalization, uPAR is itself endocytosed and recycled back to the cell surface. PMA-induced differentiation of myeloid cells is accompanied by inhibition of uPA-PAI-1 internalization/degradation and the down-regulation of alpha 2-MR. The regulation of uPAR and alpha 2-MR levels might be part of the differentiation program of myeloid cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Plasminogen Activators / metabolism
  • Receptors, Cell Surface / antagonists & inhibitors
  • Receptors, Cell Surface / metabolism*
  • Receptors, Urokinase Plasminogen Activator
  • Serpins / metabolism*
  • Urokinase-Type Plasminogen Activator / antagonists & inhibitors
  • Urokinase-Type Plasminogen Activator / metabolism*


  • PLAUR protein, human
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • Serpins
  • Plasminogen Activators
  • Urokinase-Type Plasminogen Activator