Expression of I2PP2A, inhibitor of protein phosphatase 2A, induces c-Jun and AP-1 activity

Transient expression of I-2(PP2A), a potent inhibitor of protein phosphatase 2A (PP2A), in HEK-293 cells increased the concentration and DNA binding of the proto-oncogene c-Jun. In contrast, expression of the catalytic subunit of PP2A (PP2A(C)) markedly decreased the concentration and DNA binding of c-Jun. Expression of I-2(PP2A) also increased the transcriptional activity of activator protein-1, and this effect was diminished in a dose-dependent manner by expression of PP2A(C). Densitometric analysis following Western blotting of extracts with antibodies specific for phospho-Ser(63) and Ser(73) suggests that the effects of I-2(PP2A) and PP2A(C) expression might be mediated, in part, by changes in the phosphorylation of c-Jun at Ser(63). The results indicate that I-2(PP2A) elicits effects that are consistent with it acting as an inhibitor of PP2A in intact cells, and suggest that PP2A might exhibit site selectivity with respect to c-Jun phosphorylation.