Competition between plasminogen and tissue plasminogen activator for cellular binding sites.
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.
Institut De Recerca Oncologica, Hospital Duran i Reynals, Autovia de Castelldefels, L'Hospitalet de Llobregat, Barcelona, Spain.
J
J
Felez
C J
CJ
Chanquia
P
P
Fabregas
E F
EF
Plow
L A
LA
Miles
D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D005732:Gangliosides; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D008239:Lysine