PKA negatively regulates PP2Cβ to activate NF-κB-mediated inflammatory signaling
Hyo-Kyung Choi ; Soo-Yeon Park ; Ho-Geun Yoon ; Kyung-Chul Choi ; Woo Jin Jun ; Jeongmin Lee ; Yoo-Hyun Lee ; Eun-Jeong Han ; Hye-Jeong Oh
Biochemical and Biophysical Research Communications, Vol.436(3) : 473~477, 2013
Biochemical and Biophysical Research Communications
Protein phosphatase 2Cβ (PP2Cβ) was found to act as a negative regulator of NF-κB-mediated inflammatory signaling; however, its regulatory mechanism has not been examined. Here, we show that protein kinase A (PKA) phosphorylates the PP2Cβ, which was inhibited by PKA-specific inhibitor, H89. Mutation analysis of serine residues in PP2Cβ revealed that Ser-195 in PP2Cβ is phosphorylated by PKA. Importantly, PKA inhibition by H89 abrogated the Forskolin-induced destabilization of PP2Cβ against ubiquitin-dependent proteosomal degradation pathway. Furthermore, H89 treatment efficiently reversed the negative effect of Forskolin on the anti-inflammatory function of PP2Cβ. Collectively, these data suggest that PKA destabilizes PP2Cβ upon inflammatory stimuli via phosphorylation of Ser-195 in PP2Cβ.