Competition Between Plasminogen and Tissue Plasminogen Activator for Cellular Binding Sites

• Published in: Blood Vol. 82; no. 8; pp. 2433 - 2441
• Main Authors: Felez, Jordi, Chanquia, Carlos J., Fabregas, Pere, Plow, Edward F., Miles, Lindsey A.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.10.1993; The Americain Society of Hematology
• Subjects: Binding Sites; Binding, Competitive; Biological and medical sciences; Blood coagulation. Blood cells; Cell Line; Cells, Cultured; Coagulation factors; Endothelium, Vascular - metabolism; Fundamental and applied biological sciences. Psychology; Gangliosides - metabolism; Humans; Lysine - metabolism; Molecular and cellular biology; Monocytes - metabolism; Plasminogen - metabolism; Tissue Plasminogen Activator - metabolism; Human; Cell culture; Serine endopeptidases; Enzyme; Hematopoietic cell; Binding site; Cell surface; t-Plasminogen activator; Hemostasis; Hydrolases; Plasminogen; Proteinases; Coagulation factor
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V82.8.2433.2433

Cellular receptors for plasminogen and tissue plasminogen activator (t-PA) regulate plasminogen activation and cell-associated proteolytic activity. The characteristics of the interactions of both ligands with monocytes and monocyt-oid cell lines bear certain similarities, including affinity (kd approximately 1 μmol/L) capacity and susceptibility to car-boxypeptidase treatment. Therefore, we have undertaken the present study to determine directly whether t-PA and plasminogen share common binding sites on cells. We found that recombinant human single-chain t-PA (rt-PA) could inhibit the binding of 125l-plasminogen to the cells and, conversely, plasminogen could inhibit 125l-rt-PA binding. This relationship was observed with 9 cell types, including both adherent cells and cells in suspension. In addition, under several conditions of cell treatment, plasminogen and t-PA receptor expression was modulated in parallel. Furthermore, molecules that have been implicated as candidate plasminogen receptors, gangliosides, and an α-enolase—related molecule, also interacted with t-PA. These results suggest that at least a component of the binding sites for plasminogen is shared with t-PA. Occupancy of these sites by either or both ligand(s) should result in arming the cells with the proteolytic activity of plasmin.