PKA negatively regulates PP2Cβ to activate NF-κB-mediated inflammatory signaling
PKA negatively regulates PP2Cβ to activate NF-κB-mediated inflammatory signaling
复制标题
DOI：
10.1016/j.bbrc.2013.05.129
复制
发表时间：
2013-07-05
影响因子：
3.1
通讯作者：
Yoon, Ho-Geun
中科院分区：
文献类型：
--
作者：
Choi, Hyo-Kyung;Park, Soo-Yeon;Yoon, Ho-Geun
蛋白磷酸酶2C β（PP 2C β）被发现作为NF-κ B介导的炎症信号的负调节剂：然而，其调节机制尚未研究。在这里，我们表明，蛋白激酶A（MA）磷酸化的PP 2C β，这是抑制PICA特异性抑制剂，H89。PP 2C β中丝氨酸残基的突变分析揭示PP 2C β中的Ser-195被PICA磷酸化。重要的是，PKA抑制H89废除毛喉素诱导的PP 2C β对泛素依赖性蛋白体降解途径的不稳定。此外，H89治疗有效地逆转了毛喉素对PP 2C β抗炎功能的负面影响。总的来说，这些数据表明PICA通过PP 2C β中Ser-195的磷酸化使PP 2C β在炎症刺激后不稳定。(C)2013 Elsevier Inc. All rights reserved.
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.