PKA regulates calcineurin function through the phosphorylation of RCAN1: Identification of a novel phosphorylation site

被引：13

作者：

Kim, Seon Sook ^{[1
]}

Lee, Eun Hye ^{[1
]}

Lee, Kooyeon ^{[2
]}

Jo, Su-Hyun ^{[3
]}

Seo, Su Ryeon ^{[1
]}

机构：

[1] Kangwon Natl Univ, Inst Biosci & Biotechnol, Coll Biomed Sci, Dept Mol Biosci, Chunchon 200701, South Korea

[2] Kangwon Natl Univ, Inst Biosci & Biotechnol, Coll Biomed Sci, Dept Biohlth Technol, Chunchon 200701, South Korea

[3] Kangwon Natl Univ, Inst Biosci & Biotechnol, Plus Grad Program BK21, Dept Physiol, Chunchon 200701, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2015年 / 459卷 / 04期

基金：

新加坡国家研究基金会;

关键词：

Calcineurin; RCAN1; Phosphorylation; PKA; Inflammation; CELL-ACTIVATION; GENE; NFAT; TRANSCRIPTION; EXPRESSION; CALCIUM; FAMILY;

D O I：

10.1016/j.bbrc.2015.02.155

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Calcineurin is a calcium/calmodulin-dependent phosphatase that has been implicated in T cell activation through the induction of nuclear factors of activated T cells (NFAT). We have previously suggested that endogenous regulator of calcineurin (RCAN1, also known as DSCR1) is targeted by protein kinase A (PKA) for the control of calcineurin activity. In the present study, we characterized the PKA-mediated phosphorylation site in RCAN1 by mass spectrometric analysis and revealed that PM directly phosphorylated RCAN1 at the Ser 93. PKA-induced phosphorylation and the increase in the half-life of the RCAN1 protein were prevented by the substitution of Ser 93 with Ala (S93A). Furthermore, the PKA-mediated phosphorylation of RCAN1 at Ser 93 potentiated the inhibition of calcineurin-dependent pro-inflammatory cytokine gene expression by RCAN1. Our results suggest the presence of a novel phosphorylation site in RCAN1 and that its phosphorylation influences calcineurin-dependent inflammatory target gene expression. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：604 / 609

页数：6

共 27 条

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