PR55 alpha, a regulatory subunit of PP2A, specifically regulates PP2A-mediated beta-catenin dephosphorylation.
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.
Zhang
Wen
W
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
Yang
Jun
J
Liu
Yajuan
Y
Chen
Xi
X
Yu
Tianxin
T
Jia
Jianhang
J
Liu
Chunming
C
D000818:Animals; D060466:Axin Protein; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D004331:Drosophila melanogaster; D004791:Enzyme Inhibitors / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D018021:Lithium Chloride / Q000494:pharmacology; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits; D011714:Pyrans / Q000494:pharmacology; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013141:Spiro Compounds / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism*
D060466:Axin Protein; D004791:Enzyme Inhibitors; C512974:PPP2R2A protein, human; D021122:Protein Subunits; D011714:Pyrans; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D013141:Spiro Compounds; D051176:beta Catenin; C053079:tautomycin; D019319:Okadaic Acid; D038362:Glycogen Synthase Kinase 3; D054648:Protein Phosphatase 2; D018021:Lithium Chloride