Dual-specificity phosphatases regulate mitogen-activated protein kinase signaling in adipocytes in response to inflammatory stress.
Dual-specificity phosphatases regulate mitogen-activated protein kinase signaling in adipocytes in response to inflammatory stress.
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DOI：
10.1016/j.cellsig.2018.10.011
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发表时间：
2019-01
影响因子：
4.8
通讯作者：
Morrison, Ron F.
中科院分区：
文献类型：
--
作者：
Ferguson, Bradley S.;Nam, Heesun;Morrison, Ron F.
肥胖是心脏病、胰岛素抵抗和II型糖尿病的一个强有力的预测因素。慢性低度炎症通过丝裂原活化蛋白激酶（MAPK）信号通路将肥胖和胰岛素抵抗联系起来。上游激酶激活MAPK信号传导，而MAPK特异性双特异性磷酸酶（DUSPs）充当MAPK失活（即去磷酸化）的关键调节剂和控制剂。使用3个T3-L1脂肪细胞中的肿瘤坏死因子α（TNFα）作为炎症模型，我们报告了TNFα介导的Dusp 1、Dusp 8和Dusp 16的诱导调节MAPK的瞬时调节（即，ERK、JNK和p38）磷酸化和随后的炎性基因表达。在前脂肪细胞和脂肪细胞中，检测的所有三种MAPK均被TNFα磷酸化，其中信号强度和持续时间具有表型特异性。此外，TNFα以表型特异性方式增加前脂肪细胞和脂肪细胞中DUSPs的mRNA丰度，同时伴有MAPK的去磷酸化。RNA干扰（RNAi）介导的Dusp 1、Dusp 8和Dusp 16敲低增加了ERK、JNK和p38的信号强度和持续时间，随后导致响应TNFα的MCP-1、IL-6和考克斯-2的MAPK依赖性炎症基因表达显著增加。这项研究强调了DUSPs作为MAPK信号传导和脂肪细胞炎症基因表达的组成部分的重要作用。
Obesity is a strong predictor of heart disease, insulin resistance, and type II diabetes. Chronic, low-grade inflammation links obesity and insulin resistance through mitogen-activated protein kinase (MAPK) signaling pathways. Upstream kinases activate MAPK signaling, while MAPK-specific dual-specificity phosphatases (DUSPs) act as key modulators and controllers of MAPK deactivation (i.e. dephosphorylation). Using tumor necrosis factor α (TNFα) in 3 T3-L1 adipocytes as a model of inflammation, we report that TNFα-mediated induction of Dusp1, Dusp8 and Dusp16 modulated the transient regulation of MAPK (i.e., ERK, JNK, and p38) phosphorylation and subsequent inflammatory gene expression. All three MAPKs examined were phosphorylated in preadipocytes and adipocytes in response to TNFα, where signaling magnitude and duration were phenotype-specific. Moreover, TNFα increased mRNA abundance of DUSPs in preadipocytes and adipocytes in a phenotype-specific manner, concomitant with dephosphorylation of MAPKs. RNA interference (RNAi)-mediated knockdown of Dusp1, Dusp8 and Dusp16 increased signaling magnitude and duration of ERK, JNK, and p38 that subsequently resulted in significant increases in MAPK-dependent inflammatory gene expression of MCP-1, IL-6, and Cox-2 in response to TNFα. This study highlights important roles for DUSPs as integral components of MAPK signaling and adipocyte inflammatory gene expression.
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双重特异性磷酸酶对ERK2的时空调节。
影响因子：
4.8
作者：
Caunt, Christopher J.;Armstrong, Stephen P.;Rivers, Caroline A.;Norman, Michael R.;McArdle, Craig A.
通讯作者：
McArdle, Craig A.
DOI：
10.1084/jem.20051753
发表时间：
2006-01-23
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hammer M;Mages J;Dietrich H;Servatius A;Howells N;Cato AC;Lang R
通讯作者：
Lang R
影响因子：
3.7
作者：
Chazenbalk G;Bertolotto C;Heneidi S;Jumabay M;Trivax B;Aronowitz J;Yoshimura K;Simmons CF;Dumesic DA;Azziz R
通讯作者：
Azziz R
影响因子：
7.7
作者：
Feng B;Jiao P;Helou Y;Li Y;He Q;Walters MS;Salomon A;Xu H
通讯作者：
Xu H
影响因子：
6.7
作者：
Cho, Il Je;Woo, Na Ri;Kim, Sang Geon
通讯作者：
Kim, Sang Geon