The cell-binding domains of plasminogen and their function in plasma.
Plasminogen binding sites are expressed by a wide variety of cell types and serve to promote fibrinolysis and local proteolysis. In this study, the recognition specificity of cells for plasminogen has been examined, primarily using platelets as models. Analyses with plasminogen fragments implicated residues 79-337 (or 353), comprising the first three kringles of plasminogen, as a primary recognition site for plasminogen binding to both thrombin-stimulated and nonstimulated platelets. Other regions of plasminogen, namely residues 354-439 and 442-790, can also participate in the interaction, and these other regions contribute differentially to the binding of the ligand to stimulated and nonstimulated platelets. Binding to nucleated cells, with U937 cells serving as the prototype, is dependent upon a recognition specificity similar to that of unstimulated platelets. Binding of Glu-plasminogen, the native form of the molecule, to thrombin-stimulated platelets has been shown previously to require platelet fibrin. By comparing the interaction of Glu-plasminogen and its degradation product, Lys-plasminogen, with thrombin-stimulated platelets, it is concluded that the cell surface uniquely enhances the affinity of Glu-, but not Lys-plasminogen, for fibrin. Finally, we have demonstrated that cellular receptors and interactive sites within plasminogen are available in the plasma environment. Thus, the functions ascribed to cellular plasminogen receptors can occur within a physiologic setting.
Miles
L A
LA
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Dahlberg
C M
CM
Plow
E F
EF
D001665:Binding Sites; D001667:Binding, Competitive; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002460:Cell Line; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D010196:Pancreatic Elastase / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology
D001798:Blood Proteins; D010446:Peptide Fragments; C018998:lysyl-plasminogen; D005337:Fibrin; D010958:Plasminogen; D010196:Pancreatic Elastase; D013917:Thrombin