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Differential functions of tissue factor in the trans-activation of cellular signalling pathways

Ettelaie, Camille; Li, Chao; Collier, Mary E. W.; Pradier, Amandine; Frentzou, G. Alkistis; Wood, Charlotte G.; Chetter, Ian C.; McCollum, Peter T.; Bruckdorfer, K. Richard; James, Nicola J.

Authors

Camille Ettelaie C.Ettelaie@hull.ac.uk

Chao Li

Mary E. W. Collier M.Collier@hull.ac.uk

Amandine Pradier

G. Alkistis Frentzou

Charlotte G. Wood

Ian C. Chetter

Peter T. McCollum

K. Richard Bruckdorfer

Nicola J. James

Abstract

In this study we examined the ability of tissue factor (TF) alone, or in conjunction with factor VIIa, factor Xa and TFPI in activating a number of key signalling pathways associated with cellular growth, stress and differentiation responses in human endothelial cells. We used luciferase reporter systems to demonstrate the activation of p42/44 MAPK by the TF-FVIIa complex, mediated via the PAR1 receptor. TF alone was capable of interacting with the cell surface and was sufficient to activate the JNK-SAPK pathway and subsequently AP-1, but the level of activation was enhanced by the activity of FXa on PAR1 and 2. Furthermore, the phosphorylated form of the transmembrane-cytoplasmic domain of TF was directly responsible for activation of these pathways. CREB activation occurred in response to TF-FVIIa in a non-protease dependent manner but was lowered on addition of FXa. Finally, NFκB activation occurred in response to FVIIa or FXa, with the latter exhibiting higher levels of activation. In conclusion, we have shown that TF is capable of activating differing signalling pathways, via more than one mechanism. The differential influence of TF is modified depending on the presence of other coagulation factors and ultimately acts as a deciding factor in the determination of cellular fate. © 2006 Elsevier Ireland Ltd. All rights reserved.

Journal Article Type Article
Publication Date Sep 30, 2007
Journal ATHEROSCLEROSIS
Print ISSN 0021-9150
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 194
Issue 1
Pages 88-101
Institution Citation Ettelaie, C., Li, C., Collier, M. E. W., Pradier, A., Frentzou, G. A., Wood, C. G., …James, N. J. (2007). Differential functions of tissue factor in the trans-activation of cellular signalling pathways. Atherosclerosis, 194(1), 88-101. https://doi.org/10.1016...rosclerosis.2006.10.010
DOI https://doi.org/10.1016/j.atherosclerosis.2006.10.010
Keywords Cardiology and Cardiovascular Medicine
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