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Arterioscler Thromb Vasc Biol. 2007 Jun;27(6):1447-55. Epub 2007 Apr 5.

Modulation of tissue factor-factor VIIa signaling by lipid rafts and caveolae.

Author information

1
Biomedical Research Division, The University of Texas Health Center at Tyler, 11937 US Highway 271, Tyler, TX 75708, USA.

Abstract

OBJECTIVE:

Coagulation factor VIIa (VIIa) binding to its cellular receptor, tissue factor (TF), not only initiates the coagulation cascade but also induces cell signaling by activating G-protein coupled protease-activated receptors. The objective of the present study is to investigate the role of lipid rafts and caveolae in modulating TF-VIIa signaling and coagulant functions.

METHODS AND RESULTS:

TF-VIIa coagulant function was measured in factor X activation assay and the signaling function was evaluated in phosphoinositide hydrolysis and IL-8 gene induction. Buoyant density gradient centrifugation and immunofluorescence confocal microscopy were used to determine cellular localization of TF and protease-activated receptor 2. The data show that a substantial fraction of TF and protease-activated receptor 2 resides in lipid rafts/caveolae, and disruption of lipid rafts by cholesterol depletion or modification reduced TF-VIIa-induced cell signaling. Disruption of caveolae with caveolin-1 silencing had no effect on the TF-VIIa coagulant activity but inhibited the TF-VIIa-induced cell signaling.

CONCLUSION:

Overall our data show that lipid raft/caveolae play a selective role in modulating the TF-VIIa signaling function without affecting the TF-VIIa coagulant activity.

PMID:
17413039
PMCID:
PMC2647778
DOI:
10.1161/ATVBAHA.107.143438
[Indexed for MEDLINE]
Free PMC Article
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