UROKINASE UROKINASE RECEPTOR SYSTEM - INTERNALIZATION/DEGRADATION OF UROKINASE-SERPIN COMPLEXES - MECHANISM AND REGULATION/

The urokinase-type plasminogen activator (uPA) is secreted as a single -chain inactive zymogen (pro-uPA), Upon its secretion, pro-uPA binds t o its glycosylphosphatidylinositol-anchored specific cell receptor (uP AR). The activation of pro-uPA to the active two-chain uPA is accelera ted with uPAR-bound pro-uPA and is achieved by plasmin and proteases o f 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). uP A-PAI-1 and uPA-PN-1 complexes, but not free uPA, are readily internal ized and degraded through a mechanism that involves the multiligand re ceptors alpha(2)-macroglobulin receptor/low density lipoprotein recept or-associated protein (alpha(2)-MR) and epithelial glycoprotein 330 (g p330). 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 internalizatio n/degradation and the down-regulation of alpha(2)-MR. The regulation o f uPAR and alpha(2)-MR levels might be part of the differentiation pro gram of myeloid cells.