Potential Role of Kringle-Integrin Interaction in Plasmin and uPA Actions (A Hypothesis)
Figure 1
A model of plasmin-induced cell migration and the potential mechanism of angiostatin action. uPA activates plasminogen to plasmin pericellularly. Plasmin is accumulated on the cell surface by binding to integrins and stabilized. Free plasmin would be rapidly inactivated by circulating serine protease inhibitors (e.g., -antiplasmin). The catalytic activity of plasmin on the cell surface is directly involved in signal transduction, possibly through activating G-protein coupled PARs. The binding of the kringle domain may not be directly involved in signaling through integrin pathways. Angiostatin effectively blocks plasmin-induced cell migration possibly by competing with plasmin for binding to integrins. Aprotinin, a serine protease inhibitor, also effectively blocks migration. It should be noted that other antiangiogenic agents, RGD-peptide and anti-, are effective inhibitors of this process.
