The cell biology of the plasminogen system

The plasminogen system plays a pivotal role in maintaining vascular patency and in cell migration. Binding of plasminogen to surfaces (i.e., fibrin or cells) is of crucial importance in regulating the function of this system. Plasmin(ogen) binds to cells with low affinity and high capacity via its lysine binding sites, which are associated with its kringle domains and recognize carboxy-terminal lysines of cell surface proteins. Upon binding to cellular receptors, plasminogen is more readily activated; bound plasmin has increased enzymatic activity and is protected from inactivation by inhibitors. Plasminogen receptors are modulated by numerous factors, including proteases, steroid hormones, cytokines and the adhesive state of the cells. The apoprotein(a) moiety of lipoprotein(a) is remarkably similar in amino acid sequence to plasminogen. Shared binding sites for lipoprotein(a) and plasmin(ogen) on cell surfaces and in the subendothelial matrix may contribute to the pathogenetic risks associated with elevated levels of lipoprotein(a).