Title: Fibrinogen contains cryptic PAI-1 binding sites that are exposed on binding to solid surfaces or limited proteolysis
Authors: Smolarczyk, K ×
Boncela, J
Szymanski, J
Gils, Ann
Cierniewski, CS
Smolarczyk, Katarzyna * ×
Boncela, Joanna
Szymanski, Jacek
Cierniewski, Czeslaw S #
Issue Date: Dec-2005
Publisher: Lippincott williams & wilkins
Series Title: Arteriosclerosis, Thrombosis and Vascular Biology vol:25 issue:12 pages:2679-2684
Abstract: OBJECTIVE: In this work, we identified the fibrinogen sequence that on exposure serves as the primary binding site for functionally active PAI-1 and to a lesser extent for its latent form. In contrast, this site only weakly interacts with PAI-1 substrate. METHODS AND RESULTS: The binding site is located in the N-terminal alpha (20-88) segment of fibrinogen, in the region exposed on (1) adsorption of fibrinogen to solid surfaces; (2) the release of fibrinopeptide A during thrombin conversion of fibrinogen to fibrin; and (3) plasmin degradation of fibrinogen. This region was first identified by the yeast 2-hybrid system, then its binding characteristics were evaluated using the recombinant alpha(16-120) fragment and its shorter version, the alpha(20-88) fragment, in a solid phase binding assay and plasmon surface resonance measurements. Because fibrinogen fragment E does not bind PAI-1, it suggests that sequences of Aalpha chain interacting with PAI-1 are located in the N-terminal part of the alpha(20-88) segment. CONCLUSIONS: Therefore, PAI-1 directly bound to the alpha(20-88) and thus concentrated in fibrinogen/fibrin, particularly at sites of injury and inflammation, may account for the recent observations that both its active and latent forms stimulate cell migration and wound healing.
ISSN: 1079-5642
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Pharmaceutical Biology (-)
* (joint) first author
× corresponding author
# (joint) last author

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