PAI-1: An Integrator of Cell Signaling and Migration

Figure 3

PAI-1 modulates cell migration by regulating ECM proteolysis. Physiological control of pericellular proteolysis occurs primarily through the regulation of plasminogen activation at the cell surface, which, in turn contributes to downstream MMP activity. Focal proteolysis disrupts ECM architecture, breaking cell-matrix interactions with receptors, such as integrins, and releasing bioactive fragments of extracellular matrix molecules, as well as growth factors that stimulate migratory behavior. PAI-1, through its ability to inhibit uPA-dependent activation of plasmin, titers this process maintaining the scaffolding necessary to facilitate cell migration. PAI-1: plasminogen activator inhibitor type-1, uPA: urokinase-type plasminogen activator, uPAR: uPA receptor, MMP: matrix metalloproteinase, GF: growth factor, LRP1: low-density lipoprotein receptor-related protein-1.