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PMID:19556239

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Citation

Zhang, W, Yang, J, Liu, Y, Chen, X, Yu, T, Jia, J and Liu, C (2009) PR55 alpha, a regulatory subunit of PP2A, specifically regulates PP2A-mediated beta-catenin dephosphorylation. J. Biol. Chem. 284:22649-56

Abstract

A central question in Wnt signaling is the regulation of beta-catenin phosphorylation and degradation. Multiple kinases, including CKI alpha and GSK3, are involved in beta-catenin phosphorylation. Protein phosphatases such as PP2A and PP1 have been implicated in the regulation of beta-catenin. However, which phosphatase dephosphorylates beta-catenin in vivo and how the specificity of beta-catenin dephosphorylation is regulated are not clear. In this study, we show that PP2A regulates beta-catenin phosphorylation and degradation in vivo. We demonstrate that PP2A is required for Wnt/beta-catenin signaling in Drosophila. Moreover, we have identified PR55 alpha as the regulatory subunit of PP2A that controls beta-catenin phosphorylation and degradation. PR55 alpha, but not the catalytic subunit, PP2Ac, directly interacts with beta-catenin. RNA interference knockdown of PR55 alpha elevates beta-catenin phosphorylation and decreases Wnt signaling, whereas overexpressing PR55 alpha enhances Wnt signaling. Taken together, our results suggest that PR55 alpha specifically regulates PP2A-mediated beta-catenin dephosphorylation and plays an essential role in Wnt signaling.

Links

PubMed PMC2755672 Online version:10.1074/jbc.M109.013698

Keywords

Animals; Axin Protein; Blotting, Western; Cell Line; Cell Line, Tumor; Drosophila melanogaster; Enzyme Inhibitors/pharmacology; Glycogen Synthase Kinase 3/antagonists & inhibitors; Glycogen Synthase Kinase 3/metabolism; Humans; Immunoprecipitation; Lithium Chloride/pharmacology; Okadaic Acid/pharmacology; Phosphorylation/drug effects; Protein Binding; Protein Phosphatase 2/antagonists & inhibitors; Protein Phosphatase 2/genetics; Protein Phosphatase 2/metabolism; Protein Subunits; Pyrans/pharmacology; RNA, Small Interfering; Repressor Proteins/genetics; Repressor Proteins/metabolism; Spiro Compounds/pharmacology; beta Catenin/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:PP2A

involved_in

GO:0048190: wing disc dorsal/ventral pattern formation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:PP2A

involved_in

GO:0090263: positive regulation of canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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