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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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