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Competition between plasminogen and tissue plasminogen activator for cellular binding sites

J Felez, CJ Chanquia, P Fabregas, EF Plow and LA Miles

Institut De Recerca Oncologica, Hospital Duran i Reynals, Autovia de Castelldefels, L'Hospitalet de Llobregat, Barcelona, Spain.

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 monocytoid cell lines bear certain similarities, including affinity (kd approximately 1 mumol/L) capacity and susceptibility to carboxypeptidase 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 125I-plasminogen to the cells and, conversely, plasminogen could inhibit 125I-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 alpha-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.

Volume 82, Issue 8, pp. 2433-2441, 10/15/1993
Copyright © 1993 by The American Society of Hematology


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