Back to Search
Start Over
Differential functions of tissue factor in the trans-activation of cellular signalling pathways.
- Source :
-
Atherosclerosis [Atherosclerosis] 2007 Sep; Vol. 194 (1), pp. 88-101. Date of Electronic Publication: 2006 Nov 29. - Publication Year :
- 2007
-
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, NFkappaB 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.
- Subjects :
- Cells, Cultured
Cyclic AMP Response Element-Binding Protein metabolism
Drug Synergism
Endothelial Cells cytology
Endothelium, Vascular cytology
Factor VIIa metabolism
Factor VIIa pharmacology
Factor Xa metabolism
Factor Xa pharmacology
Flow Cytometry
Humans
JNK Mitogen-Activated Protein Kinases metabolism
Lipoproteins metabolism
Lipoproteins pharmacology
Luciferases genetics
MAP Kinase Signaling System drug effects
Mitogen-Activated Protein Kinase 1 metabolism
Mitogen-Activated Protein Kinase 3 metabolism
NF-kappa B metabolism
Thromboplastin genetics
Thromboplastin pharmacology
Transcription Factor AP-1 metabolism
Transfection
Umbilical Veins cytology
Endothelial Cells metabolism
MAP Kinase Signaling System physiology
Thromboplastin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-1484
- Volume :
- 194
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Atherosclerosis
- Publication Type :
- Academic Journal
- Accession number :
- 17137581
- Full Text :
- https://doi.org/10.1016/j.atherosclerosis.2006.10.010