4 324

Cited 7 times in

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

Authors
 Hyo-Kyung Choi  ;  Soo-Yeon Park  ;  Hye-Jeong Oh  ;  Eun-Jeong Han  ;  Yoo-Hyun Lee  ;  Jeongmin Lee  ;  Woo Jin Jun  ;  Kyung-Chul Choi  ;  Ho-Geun Yoon 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.436(3) : 473-477, 2013 
Journal Title
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 
ISSN
 0006-291X 
Issue Date
2013
MeSH
Colforsin/pharmacology ; Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors ; Cyclic AMP-Dependent Protein Kinases/metabolism* ; Enzyme Stability ; Gene Expression Regulation, Enzymologic* ; HEK293 Cells ; Humans ; Inflammation/immunology ; Inflammation/pathology* ; Intracellular Signaling Peptides and Proteins/pharmacology ; Isoquinolines/pharmacology ; NF-kappa B/immunology* ; NF-kappa B/metabolism ; Phosphoprotein Phosphatases/antagonists & inhibitors ; Phosphoprotein Phosphatases/immunology* ; Phosphorylation ; Protein Phosphatase 2C ; Proteolysis ; Serine/metabolism ; Signal Transduction ; Sulfonamides/pharmacology ; Tumor Necrosis Factor-alpha/pharmacology ; Ubiquitin/metabolism
Keywords
Cytokines ; Inflammation ; NF-κB ; Protein kinase A ; Protein phosphatase 2Cβ ; Ubiquitin-dependent proteasomal degradation
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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X13009479
DOI
10.1016/j.bbrc.2013.05.129
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Park, Soo Yeon(박수연) ORCID logo https://orcid.org/0000-0003-3743-9554
Yoon, Ho Geun(윤호근) ORCID logo https://orcid.org/0000-0003-2718-3372
Choi, Hyo Kyoung(최효경)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/87056
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse