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Identification of Novel Downstream Molecules of Tissue Factor Activation by Comparative Proteomic Analysis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
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2014 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 13, no 2, 477-488 p.Article in journal (Refereed) Published
Abstract [en]

Tissue factor (TF) is both an initiator of blood coagulation and a signaling receptor. Using a proteomic approach, we investigated the role of TF in cell signaling when stimulated by its ligand, activated factor VII (FVIIa). From a 2-D difference gel electrophoresis (DIGE) study we found forty one spots that were differentially regulated over time in FVIIa stimulated cells or in comparison to nonstimulated cells. Mass spectrometry identifies 23 out of these as 13 different proteins. One of them, elongation factor 2 (EF-2), was investigated in greater detail by Western blot, a protein synthesis assay and cell cycle analysis. When tissue factor was stimulated by FVIIa, the phosphorylation of EF-2 increased which inactivates this protein. Analyzing the effect using site inactivated FVIIa (FVIIai), as well as the protease activated receptor 2 (PAR-2) agonist SLIGKV, indicated that the inactivation was not PAR-2 dependent. A panel of tissue factor mutants was analyzed further to try to pinpoint what part of the cytoplasmic domain that is needed for this effect. Performing a protein synthesis assay in two different cell lines we could confirm that protein synthesis decreased upon stimulation by FVIIa. Cell cycle analysis showed that FVIIa also promotes a higher degree of cell proliferation.

Place, publisher, year, edition, pages
2014. Vol. 13, no 2, 477-488 p.
Keyword [en]
2-D DIGE, elongation factor 2, intracellular signaling, protein synthesis, tissue factor
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-221014DOI: 10.1021/pr4006298ISI: 000331164100013OAI: oai:DiVA.org:uu-221014DiVA: diva2:707532
Available from: 2014-03-24 Created: 2014-03-24 Last updated: 2017-12-05Bibliographically approved

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Kask, LenaAlfredsson, JennyEk, BoBergquist, JonasSiegbahn, Agneta

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