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Thromb Haemost 2005; 93(01): 27-34
DOI: 10.1160/TH04-07-0405
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Regulation of chemotaxis by the cytoplasmic domain of tissue factor

Agneta Siegbahn
1   Department of Medical Sciences, Clinical Chemistry, Akademiska Hospital and Ludwig Institute for Cancer Research, Biomedical Centre, Uppsala Sweden, Haemostasis Biology, Health Care Discovery, Novo Nordisk A/S, Maaloev, Denmark
,
Matilda Johnell
1   Department of Medical Sciences, Clinical Chemistry, Akademiska Hospital and Ludwig Institute for Cancer Research, Biomedical Centre, Uppsala Sweden, Haemostasis Biology, Health Care Discovery, Novo Nordisk A/S, Maaloev, Denmark
,
Brit B. Sorensen
1   Department of Medical Sciences, Clinical Chemistry, Akademiska Hospital and Ludwig Institute for Cancer Research, Biomedical Centre, Uppsala Sweden, Haemostasis Biology, Health Care Discovery, Novo Nordisk A/S, Maaloev, Denmark
,
Lars C. Petersen
1   Department of Medical Sciences, Clinical Chemistry, Akademiska Hospital and Ludwig Institute for Cancer Research, Biomedical Centre, Uppsala Sweden, Haemostasis Biology, Health Care Discovery, Novo Nordisk A/S, Maaloev, Denmark
,
Carl-Henrik Heldin
1   Department of Medical Sciences, Clinical Chemistry, Akademiska Hospital and Ludwig Institute for Cancer Research, Biomedical Centre, Uppsala Sweden, Haemostasis Biology, Health Care Discovery, Novo Nordisk A/S, Maaloev, Denmark
› Author AffiliationsFinancial support: Supported by Swedish Research Council, Swedish Cancer Foundation, Swedish Heart and Lung Foundation and King Gustav V and Queen Victoria Foundation
Further Information

Publication History

Received 02 July 2004

Accepted after revision 21 October 2004

Publication Date:
14 December 2017 (online)

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Summary

We previously demonstrated that FVIIa bound to tissue factor (TF) induces a hyperchemotactic response towards PDGF-BB. The aim of the present study was to investigate the role of the cytoplasmic domain of TF in cell migration. Porcine aortic endothelial (PAE) cells expressing human PDGF β -receptors (PAE/ PDGFR β ) were transfected for expression of human wildtype TF (PAE/PDGFRβ ,TF), a construct lacking the cytoplasmic domain (PAE/PDGFRβ ,TF ∆ cyto), a construct with alanine replacement of serine 258 (PAE/PDGFRβ ,TFS258A), or a construct with alanine replacement of serine 253, 258 and 263 in the cytoplasmic domain (PAE/PDGFRβ ,TF3SA). All stably transfected cell lines expressed functional TF. Chemotaxis was analyzed in a modified Boyden chamber assay. PAE/PDGFRβ ,TF cells stinulated with FVIIa migrated towards a 100-fold lower concentration of PDGF-BB than in the absence of FVIIa,however,hyperchemotaxis was not seen in PAE/PDGFRβ ,TF ∆ cyto cells. PAE/ PDGFR β /TFS258A and PAE/PDGFRβ ,TF3SA cells responded to low levels of PDGF-BB, but migrated a significantly shorter distance than PAE/PDGFRβ ,TF cells. Thus, hyperchemotaxis towards PDGF-BB is likely to depend in part on phosphorylation of the cytoplasmic domain of TF.We conclude that the cytoplasmic domain of TF plays a pivotal role in modulating cellular migration response.Our results suggest that the FVIIa/TF complex mediates intracellular signaling by alternative signal transduction pathway(s).

Keywords

Tissue factor - platelet-derived growth factor - intracellular signaling - cell migration
 

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