Possible involvement of protein phosphatase type 2A in tumor necrosis factor alpha-induced tissue factor expression...

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.