Regulation of cell adhesion by PAI-1

Type I plasminogen activator inhibitor (PAI‐1) is the primary inhibitor of tissue‐and urokinase‐type plasminogen activators. It circulates in plasma complexed with vitronectin (VN), the primary PAI‐1 binding protein. The somatomedin B (SMB) domain of VN contains both the high affinity PAI‐1 binding site and the specific site for urokinase plasminogen activator receptor (uPAR). PAI‐1 is able to regulate uPAR‐mediated cell adhesion by competing with uPAR for VN binding. Binding of PAI‐1 to SMD may also affect integrin‐mediated cell adhesion to VN by hindering integrin binding to the RGD sequence adjacent to the uPAR binding site.