Tissue plasminogen activator catalyzed Lys-Plasminogen activation on heparin-inserted phospholipid liposomes

Biochemistry ◽  
1990 ◽  
Vol 29 (21) ◽  
pp. 5188-5194 ◽  
Author(s):  
Shinji Soeda ◽  
Shinya Sakaguchi ◽  
Hiroshi Shimeno ◽  
Atsuo Nagamatsu
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Plasminogen Activation ◽  
Phospholipid Liposomes ◽  
Tissue Plasminogen

scholarly journals Tissue plasminogen activator is a ligand of cation-independent mannose 6-phosphate receptor and consists of glycoforms that contain mannose 6-phosphate

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
James J. Miller ◽  
Richard N. Bohnsack ◽  
Linda J. Olson ◽  
Mayumi Ishihara ◽  
Kazuhiro Aoki ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Dependent Manner ◽  
Plasminogen Activation ◽  
Urokinase Plasminogen Activator Receptor ◽  
Plasminogen Activation System ◽  
Extracellular Region ◽  
Glycosylation Sites ◽  
Tissue Plasminogen ◽  
Mannose 6 Phosphate

AbstractPlasmin is the key enzyme in fibrinolysis. Upon interaction with plasminogen activators, the zymogen plasminogen is converted to active plasmin. Some studies indicate plasminogen activation is regulated by cation-independent mannose 6-phosphate receptor (CI-MPR), a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation. Plasminogen regulation may be accomplished by CI-MPR binding to plasminogen or urokinase plasminogen activator receptor. We asked whether other members of the plasminogen activation system, such as tissue plasminogen activator (tPA), also interact with CI-MPR. Because tPA is a glycoprotein with three N-linked glycosylation sites, we hypothesized that tPA contains mannose 6-phosphate (M6P) and binds CI-MPR in a M6P-dependent manner. Using surface plasmon resonance, we found that two sources of tPA bound the extracellular region of human and bovine CI-MPR with low-mid nanomolar affinities. Binding was partially inhibited with phosphatase treatment or M6P. Subsequent studies revealed that the five N-terminal domains of CI-MPR were sufficient for tPA binding, and this interaction was also partially mediated by M6P. The three glycosylation sites of tPA were analyzed by mass spectrometry, and glycoforms containing M6P and M6P-N-acetylglucosamine were identified at position N448 of tPA. In summary, we found that tPA contains M6P and is a CI-MPR ligand.

The potentiating effect of platelet on plasminogen activation by tissue plasminogen activator

1985 ◽  
Vol 40 (6) ◽  
pp. 853-861 ◽  
Author(s):  
K. Deguchi ◽  
S. Murashima ◽  
S. Shirakawa ◽  
C. Soria ◽  
J. Soria ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Plasminogen Activation ◽  
Tissue Plasminogen

scholarly journals β2-glycoprotein i is a cofactor for tissue plasminogen activator-mediated plasminogen activation

2009 ◽  
Vol 60 (2) ◽  
pp. 559-568 ◽  
Author(s):  
Chunya Bu ◽  
Lei Gao ◽  
Weidong Xie ◽  
Jainwei Zhang ◽  
Yuhong He ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Plasminogen Activation ◽  
Glycoprotein I ◽  
Tissue Plasminogen

scholarly journals The cartilage-specific lectin C-type lectin domain family 3 member A (CLEC3A) enhances tissue plasminogen activator–mediated plasminogen activation

2017 ◽  
Vol 293 (1) ◽  
pp. 203-214 ◽  
Author(s):  
Daniela Lau ◽  
Dzemal Elezagic ◽  
Gabriele Hermes ◽  
Matthias Mörgelin ◽  
Alexander P. Wohl ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Plasminogen Activation ◽  
Domain Family ◽  
Lectin Domain ◽  
Tissue Plasminogen

Kinetics Of Plasminogen Activation By Tissue Plasminogen Activator. Role Of Fibrin

1981 ◽  
Author(s):  
M Hoylaerts ◽  
D C Rijken ◽  
H R Lijnen ◽  
D Collen
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Catalytic Efficiency ◽  
Reaction Scheme ◽  
Plasminogen Activation ◽  
Catalytic Rate Constant ◽  
Activation Rate ◽  
Tissue Plasminogen ◽  
Human Plasminogen ◽  
Straight Lines

The activation of human plasminogen (P) by two-chain tissue plasminogen activator (A) was studied in the presence of fibrin films (F) of increasing size and surface density. Initial rates of plasminogen activation (v) were determined as a function both of the plasminogen and fibrin concentration. The activation rate was strongly dependent on the presence of fibrin and plots of 1/v versus 1/ [p] or 1 /[F] yielded straight lines. The kinetic data were in agreement with the following reaction scheme.According to this model tissue plasminogen activator would bind to fibrin with a dissociation constant (KF of 0.2 µM and this complex fixes plasminogen with a Michaelis constant (Kp’) of 0.15 µM (Glu-plasminogen) or 0.02 µM (Lys-plasminogen) to form a ternary complex, converted to plasmin with a catalytic rate constant kcat = 0.05 s-1. This mechanism implies that both plasminogen and tissue plasminogen activator are concentrated on the fibrin surface through formation of a fibrin bridge. Activation of plasminogen in the absence of fibrin occurs with Km = 65 µM (Glu-plasminogen) or Km= 19 µM (Lys-plasminogen) and kcat = 0.05 s-1. Our data suggest that fibrin enhances the activation rate of plasminogen by tissue plasminogen activator by increasing the affinity of plasminogen for fibrin-bound tissue plasminogen activator and not by influencing the catalytic efficiency of the enzµMe. These data also support the hypothesis that fibrinolysis is both triggered by and directed towards fibrin.Generated plasmin was quantitated by measuring the rate of solubilization of 125I-labeled fibrin.

scholarly journals Zymogen-activation kinetics. Modulatory effects of trans-4-(aminomethyl)cyclohexane-1-carboxylic acid and poly-d-lysine on plasminogen activation

1985 ◽  
Vol 225 (1) ◽  
pp. 149-158 ◽  
Author(s):  
L C Petersen ◽  
J Brender ◽  
E Suenson
Keyword(s):  
Carboxylic Acid ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Plasminogen Activation ◽  
Zymogen Activation ◽  
Activation Kinetics ◽  
Progress Curve ◽  
Plasminogen Activator System ◽  
Tissue Plasminogen ◽  
Kinetics Of

The kinetics of plasminogen activation catalysed by urokinase and tissue-type plasminogen activator were investigated. Kinetic measurements are performed by means of a specific chromogenic peptide substrate for plasmin, D-valyl-L-leucyl-L-lysine 4-nitroanilide. Two methods are proposed for the analysis of the resulting progress curve of nitroaniline formation in terms of zymogen-activation kinetics: a graphical transformation of the parabolic curve and transformation of the curve for nitroaniline production into a linear progress curve by the addition of a specific inhibitor of plasmin, bovine pancreatic trypsin inhibitor. The two methods give similar results, suggesting that the reaction between activator and plasminogen is a simple second-order reaction at least at plasminogen concentrations up to about 10 microM. The kinetics of both Glu1-plasminogen (residues 1-790) and Lys77-plasminogen (residues 77-790) activation were investigated. The results confirm previous observations showing that trans-4-(aminomethyl)cyclohexane-1-carboxylic acid at relatively low concentrations enhances the activation rate of Glu1-plasminogen but not that of Lys77-plasminogen. At higher concentrations both Glu1- and Lys77-plasminogen activation are inhibited. The concentration interval for the inhibition of urokinase-catalysed reactions is shown to be very different from that of the tissue-plasminogen activator system. Evidence is presented indicating that binding to the active site of urokinase (KD = 2.0 mM) is responsible for the inhibition of the urokinase system, binding to the active site of tissue-plasminogen activator is approx. 100-fold weaker, and inhibition of the tissue-plasminogen activator system, when monitored by plasmin activity, is mainly due to plasmin inhibition. Poly-D-lysine (Mr 160 000) causes a marked enhancement of plasminogen activation catalysed by tissue-plasminogen activator but not by urokinase. Bell-shaped curves of enhancement as a function of the logarithm of poly-D-lysine concentration are obtained for both Glu1- and Lys77-plasminogen activation, with a maximal effect at about 10 mg/litre. The enhancement of Glu1-plasminogen activation exerted by trans-4-(aminomethyl)cyclohexane-1-carboxylic acid is additive to that of poly-D-lysine, whereas poly-D-lysine-induced enhancement of Lys77-plasminogen activation is abolished by trans-4-(aminomethyl)cyclohexane-1-carboxylic acid. Analogies are drawn up between the effector functions of poly-D-lysine and fibrin on the catalytic activity of tissue-plasminogen activator.

Glycated Proteins Modulate Tissue–Plasminogen Activator-Catalyzed Plasminogen Activation

1997 ◽  
Vol 240 (3) ◽  
pp. 595-601 ◽  
Author(s):  
Inge W.G. Bobbink ◽  
Winnie L.H. Tekelenburg ◽  
Jan J. Sixma ◽  
Hetty C. de Boer ◽  
Jan-Dirk Banga ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Plasminogen Activation ◽  
Glycated Proteins ◽  
Tissue Plasminogen
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