597927.fig.003
Figure 3: Regulation of uPA activity and uPAR recycling. ScuPA binds to its cell surface receptor uPAR and can be activated by Plm; activated uPA in turn is inhibited by PAI1 forming a complex with LPR1 which triggers the relocalization of uPA/uPAR into clathrin coated pits. In that moment, the activation of plasmin and degradation and invasion of extracellular matrix are reduced. The quaternary complex is internalized and uPA and PAI-1 are subjected to lysosomal degradation, while uPAR and LRP1 are recycled to new places in the plasmatic membrane, which could promote further new cycle of pericellular proteolysis enhancing extracellular matrix degradation, cell invasion, and metastasis.