Title: On the molecular interactions between fibrin, tissue-type plasminogen activator and plasminogen
Authors: Lijnen, Roger ×
Van Hoef, B
Collen, Desire #
Issue Date: Apr-1990
Series Title: Thrombosis research. Supplement vol:10 pages:45-54
Abstract: The molecular interactions involved in the fibrin-mediated stimulation of plasminogen activation by tissue-type plasminogen activator (t-PA) were studied using natural human plasminogen (nPlg) and rPlg-Ala740, a recombinant human plasminogen in which the catalytic site is destroyed by mutagenesis of the active site Ser740 to Ala. Using this rPlg-Ala740 moiety, the dissociation constant of the interaction between plasminogen and CNBr-digested fibrinogen was determined to be 0.40 microM. In addition, conversion of 125I-labeled single chain plasminogen to two chain plasmin by single chain recombinant t-PA (rt-PA) in the absence or the presence of CNBr-digested fibrinogen was quantitated on reduced SDS-gel electrophoresis, combined with autoradiography and radioisotope counting of gel bands. In the absence of fibrin, the activation rate of nPlg and rPlg-Ala740 by single-chain rt-PA was comparable. In the presence of fibrin, however, the activation rate of rPlg-Ala740 was about 20-fold lower than that of nPlg. These results with rPlg-Ala740 may be explained by an impaired formation of the stable cyclic ternary complex between plasminogen, t-PA and fibrin, which mediates the fibrin stimulation of plasminogen activation by t-PA or, alternatively, by impaired conversion of single chain rt-PA to two chain rt-PA at the fibrin surface.
ISSN: 0049-3848
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science