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

被引：17

作者：

Choi, Hyo-Kyung ^{[1
]}

Park, Soo-Yeon ^{[1
]}

Oh, Hye-Jeong ^{[1
]}

Han, Eun-Jeong ^{[1
]}

Lee, Yoo-Hyun ^{[2
]}

Lee, Jeongmin ^{[3
]}

Jun, Woo Jin ^{[4
]}

Choi, Kyung-Chul ^{[5
]}

Yoon, Ho-Geun ^{[1
]}

机构：

[1] Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21, Ctr Chron Metab Dis Res,Dept Biochem & Mol Biol, Seoul 120749, South Korea

[2] Univ Suwon, Dept Food Sci & Nutr, Kyonggi Do 445743, South Korea

[3] Kyung Hee Univ, Dept Med Nutr, Yongin 446701, Kyunggi Do, South Korea

[4] Chonnam Natl Univ, Dept Food & Nutr, Kwangju, South Korea

[5] Univ Ulsan, Grad Sch, Dept Med, Seoul 138736, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2013年 / 436卷 / 03期

基金：

新加坡国家研究基金会;

关键词：

Protein phosphatase 2C beta; Protein kinase A; Inflammation; NF-kappa B; Cytokines; Ubiquitin-dependent proteasomal degradation; TRANSCRIPTIONAL ACTIVITY; RELA PHOSPHORYLATION; P65; SUBUNIT; PHOSPHATASES; ACETYLATION; KINASE-1;

D O I：

10.1016/j.bbrc.2013.05.129

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Protein phosphatase 2C beta (PP2C beta) was found to act as a negative regulator of NF-kappa B-mediated inflammatory signaling: however, its regulatory mechanism has not been examined. Here, we show that protein kinase A (MA) phosphorylates the PP2C beta, which was inhibited by PICA-specific inhibitor, H89. Mutation analysis of serine residues in PP2C beta revealed that Ser-195 in PP2C beta is phosphorylated by PICA. Importantly, PKA inhibition by H89 abrogated the Forskolin-induced destabilization of PP2C beta against ubiquitin-dependent proteosomal degradation pathway. Furthermore, H89 treatment efficiently reversed the negative effect of Forskolin on the anti-inflammatory function of PP2C beta. Collectively, these data suggest that PICA destabilizes PP2C beta upon inflammatory stimuli via phosphorylation of Ser-195 in PP2C beta. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：473 / 477

页数：5

共 14 条

[1]

Regulation of NF-κB RelA phosphorylation and transcriptional activity by p21ras and protein kinase Cζ in primary endothelial cells [J].