Possible involvement of protein phosphatase type 2A in tumor necrosis factor alpha-induced tissue factor expression in endothelial cells
- S Nagaya
- K Nakai
- M Shimura
- Y Suzuki
- H Shiku
- M Nishikawa
Affiliations: MIE UNIV,SCH MED,DEPT INTERNAL MED 2,TSU,MIE 514,JAPAN.
- Published online on: March 1, 1997 https://doi.org/10.3892/ijo.10.3.443
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The involvement of protein Ser/Thr phosphatase types 2A (PP2A) and 1 (PP1) in tumor necrosis factor alpha (TNF alpha)-induced tissue factor (TF) expression of human umbilical vein endothelial cells (HUVEC) was investigated. PP2A was more abundant than PP1 in the cytosol of HUVEC. CAL-A (0.5 nM) and OKA (2 nM), cell permeable inhibitors of PP1 and PP2A, augmented TNF alpha-induced TF expression, although TF expression induced by either TPA or thrombin was unchanged in the presence of GAL-A. Addition of CAL-A (0.5 nM) to TNF alpha-stimulated cultures led to an increase in the accumulation of TF transcripts. CAL-A (0.5 nM) also augmented the TNF alpha-induced phosphorylation of I kappa B-alpha, an inhibitor of NF-kappa B. Since PP2A is more sensitive to OKA than PP1, these results suggest that PP2A may be involved in regulating TNF alpha-induced TF expression in HUVEC through I kappa B-alpha dephosphorylation.