Dishevelled2 De-phosphorylation by PP2A is Largely Mediated by B’ family Regulatory Subunits

Dishevelled2 (Dvl2) is a key protein factor in Wnt signaling and is intensely regulated by phosphorylation. Protein phosphatase 2A (PP2A), a phosphatase of Dvl2, participates in the regulation of Dvl2 via de-phosphorylation. There are 16 regulatory subunits in PP2A in total, which determine the substrate specificity of PP2A. However, no comprehensive study has been conducted on these regulatory subunits to clearly decipher those involved in de-phosphorylation of Dvl2. Through siRNA-based knocking down of each PP2A regulatory subunit gene in one cell line, we analyzed all regulatory subunits’ roles in regulating the de-phosphorylation of Dvl2. It turned out that multiple PP2A regulatory subunits were involved in the regulation of de-phosphorylation of Dvl2, especially for members of B’ family regulatory subunits. All members in B’ family were involved, contributing as the predominant regulatory subunits. Cell co-localization and co-immunoprecipitation experiments also confirmed the regulatory roles in Dvl2 de-phosphorylation played by PP2A B’ regulatory subunits. In summary, this study clarifies the specific PP2A regulatory subunits participating in the regulation of Dvl2 de-phosphorylation and facilitates the understanding of the cellular functions of PP2A regulatory subunits and their relationships with substrates.

CSTR: 32200.14.cjcb.2019.09.0006