A positive role for the PP2A catalytic subunit in Wnt signal transduction

Protein phosphatase-2A (PP2A) is a multisubunit serine/threonine phosphatas e involved in intracellular signaling, gene regulation, and cell cycle prog ression. Different, subunits of PP2A bind to Axin and Adenomatous Polyposis Coli, components of the Wnt signal transduction pathway. Using early Xenop us embryos, we studied how PP2A functions in Wnt signal transduction. The c atalytic subunit of PP2A (PP2A-C) potentiated secondary axis induction and Siamois reporter gene activation by Dishevelled, a component of the Wnt pat hway, indicating a: positive regulatory role of this enzyme in Wnt signalin g. in contrast, small t antigen, an antagonist of PP2A-C, inhibited Disheve lled-mediated signal transduction, as did the regulatory PP2A-B'epsilon sub unit, consistent with the requirement of PP2A function in this pathway. Alt hough Wnt signaling is thought to occur via regulation of beta -catenin deg radation, PP2A-C did not significantly affect beta -catenin stability. More over, the pathway activated by a stabilized form of beta -catenin was sensi tive to PP2A-C and its inhibitors, suggesting that PP2A-C acts downstream o f beta -catenin. Because previous work has suggested that PP2A can act upst ream of beta -catenin, we propose that PP2A regulates the Wnt pathway at mu ltiple levels.