Further characterization of the cellular plasminogen binding site: evidence that plasminogen 2 and lipoprotein a compete for the same site.
Specific cell surface receptors for plasminogen (Pg) are expressed by a wide variety of cell types and serve to promote fibrinolysis and local Pg proteolysis. Pg types 1 and 2, separated by chromatography on concanavalin A-Sepharose, were utilized to determine their binding to the monocytoid U937 cell line. Both forms bind in a dose-dependent manner. However, Pg 2 binds to the cellular receptor considerably better than Pg 1 and at equilibrium demonstrates approximately 10-fold greater binding. Lipoprotein a [Lp(a)], which possesses a subunit showing considerable homology to Pg, competes with Pg 2 for the Pg receptor in U937 cells. Moreover, Pg 1 is not able to displace Pg 2 from the receptor. These studies suggest that high levels of Lp(a) may alter the profibrinolytic activity at the cell surface and increase the risks of atherosclerosis and thrombosis. This hypothesis is in accord with the 2-5-fold increased risk of atherosclerosis in patients having high levels of Lp(a).
Gonzalez-Gronow
M
M
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710.
Edelberg
J M
JM
Pizzo
S V
SV
D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D005342:Fibrinolysis; D006801:Humans; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000378:metabolism*; D010958:Plasminogen / Q000302:isolation & purification / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator
D017270:Lipoprotein(a); D008074:Lipoproteins; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010958:Plasminogen