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PKA negatively regulates PP2Cβ to activate NF-κB-mediated inflammatory signaling

Title
 PKA negatively regulates PP2Cβ to activate NF-κB-mediated inflammatory signaling 
Authors
 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 
Issue Date
2013
Journal Title
 Biochemical and Biophysical Research Communications 
ISSN
 0006-291X 
Citation
 Biochemical and Biophysical Research Communications, Vol.436(3) : 473~477, 2013 
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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/87056
DOI
10.1016/j.bbrc.2013.05.129
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Biochemistry & Molecular Biology
Yonsei Authors
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Link
 http://www.sciencedirect.com/science/article/pii/S0006291X13009479
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