JBC INTERFERin siRNA transfection reagent

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Stewart, R. J.
Right arrow Articles by Weitz, J. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stewart, R. J.
Right arrow Articles by Weitz, J. I.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

J Biol Chem, Vol. 273, Issue 29, 18292-18299, July 17, 1998

Characterization of the Interactions of Plasminogen and Tissue and Vampire Bat Plasminogen Activators with Fibrinogen, Fibrin, and the Complex of D-Dimer Noncovalently Linked to Fragment E

Ronald J. Stewart, James C. Fredenburgh, and Jeffrey I. Weitz

From Hamilton Civic Hospitals Research Centre and McMaster University, Hamilton, Ontario, L8V 1C3 Canada

Vampire bat plasminogen activator (b-PA) causes less fibrinogen (Fg) consumption than tissue-type plasminogen activator (t-PA). Herein, we demonstrate that this occurs because the complex of D-dimer noncovalently linked to fragment E ((DD)E), the most abundant degradation product of cross-linked fibrin, as well as Fg, stimulate plasminogen (Pg) activation by t-PA more than b-PA. To explain these findings, we characterized the interactions of t-PA, b-PA, Lys-Pg, and Glu-Pg with Fg and (DD)E using right angle light scattering spectroscopy. In addition, interactions with fibrin were determined by clotting Fg in the presence of various amounts of t-PA, b-PA, Lys-Pg, or Glu-Pg and quantifying unbound material in the supernatant after centrifugation. Glu-Pg and Lys-Pg bind fibrin with Kd values of 13 and 0.13 µM, respectively. t-PA binds fibrin through two classes of sites with Kd values of 0.05 and 2.6 µM, respectively. The second kringle (K2) of t-PA mediates the low affinity binding that is eliminated with epsilon -amino-n-caproic acid. In contrast, b-PA binds fibrin through a single kringle-independent site with a Kd of 0.15 µM. t-PA competes with b-PA for fibrin binding, indicating that both activators share the same finger-dependent site on fibrin. Glu-Pg binds (DD)E with a Kd of 5.4 µM. Lys-Pg binds to (DD)E and Fg with Kd values of 0.03 and 0.23 µM, respectively. t-PA binds to (DD)E and Fg with Kd values of 0.02 and 0.76 µM, respectively; interactions were eliminated with epsilon -amino-n-caproic acid, consistent with K2-dependent binding. Because it lacks a K2-domain, b-PA does not bind to either (DD)E or Fg, thereby explaining why b-PA is more fibrin-specific than t-PA.

Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 ChestHome page
J. I. Weitz, J. Hirsh, and M. M. Samama
New Antithrombotic Drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
Chest, June 1, 2008; 133(6_suppl): 234S - 256S.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. F. B. G. Gebbink, E. E. Voest, and A. Reijerkerk
Do antiangiogenic protein fragments have amyloid properties?
Blood, September 15, 2004; 104(6): 1601 - 1605.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
I. Y. Sazonova, B. R. Robinson, I. P. Gladysheva, F. J. Castellino, and G. L. Reed
{alpha} Domain Deletion Converts Streptokinase into a Fibrin-dependent Plasminogen Activator through Mechanisms Akin to Staphylokinase and Tissue Plasminogen Activator
J. Biol. Chem., June 11, 2004; 279(24): 24994 - 25001.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. J. Stewart, J. C. Fredenburgh, B. A. Leslie, B. A. Keyt, J. A. Rischke, and J. I. Weitz
Identification of the Mechanism Responsible for the Increased Fibrin Specificity of TNK-Tissue Plasminogen Activator Relative to Tissue Plasminogen Activator
J. Biol. Chem., March 31, 2000; 275(14): 10112 - 10120.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. J. Stewart, J. C. Fredenburgh, J. A. Rischke, L. Bajzar, and J. I. Weitz
Thrombin-activable Fibrinolysis Inhibitor Attenuates (DD)E-mediated Stimulation of Plasminogen Activation by Reducing the Affinity of (DD)E for Tissue Plasminogen Activator. A POTENTIAL MECHANISM FOR ENHANCING THE FIBRIN SPECIFICITY OF TISSUE PLASMINOGEN ACTIVATOR
J. Biol. Chem., November 17, 2000; 275(47): 36612 - 36620.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. B. Walker and M. E. Nesheim
A Kinetic Analysis of the Tissue Plasminogen Activator and DSPAalpha 1 Cofactor Activities of Untreated and TAFIa-treated Soluble Fibrin Degradation Products of Varying Size
J. Biol. Chem., January 26, 2001; 276(5): 3138 - 3148.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 1998 by the American Society for Biochemistry and Molecular Biology.