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Updated: May 10, 2026

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
Published on: November 2, 2018
PKA negatively regulates PP2Cβ to activate NF-κB-mediated inflammatory signaling
Hyo-Kyung Choi1, Soo-Yeon Park, Hye-Jeong Oh
1Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul, South Korea.
Abstract:
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.
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