Acetylation of MKP-1 and the control of inflammation.
Acetylation of MKP-1 and the control of inflammation.
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DOI：
10.1126/scisignal.141pe44
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发表时间：
2008-10-14
影响因子：
7.3
通讯作者：
Flavell, Richard A.
中科院分区：
文献类型：
--
作者：
Chi, Hongbo;Flavell, Richard A.
Toll样受体（TLR）是一类模式识别受体，其介导的天然免疫应答在防御微生物病原体中起着关键作用。然而，过度的TLR介导的应答导致败血症、自身免疫和慢性炎症。为了防止TLR的有害激活，细胞已经进化出多种抑制先天免疫反应的机制。TLR的刺激诱导编码促分裂原活化蛋白激酶（MAPK）磷酸酶-1（MKP-1）的基因的表达，MKP-1是一种优先使p38 MAPK和c-Jun N-末端激酶（JNK）去磷酸化的核定位的双特异性磷酸酶，导致TLR触发的促炎细胞因子的产生减弱。MKP-1通过多种机制进行后修饰，包括磷酸化。现在的一项研究表明，MKP-1在刺激TLR后也在关键赖氨酸残基上乙酰化。MKP-1的乙酰化促进了MKP-1与其底物p38 MAPK的相互作用，从而导致p38 MAPK的去磷酸化和天然免疫的抑制。
Innate immune responses mediated by Toll-like receptors (TLRs), a class of pattern-recognition receptors, play a critical role in the defense against microbial pathogens. However, excessive TLR-mediated responses result in sepsis, autoimmunity, and chronic inflammation. To prevent deleterious activation of TLRs, cells have evolved multiple mechanisms that inhibit innate immune reactions. Stimulation of TLRs induces the expression of the gene encoding the mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), a nuclear-localized dual-specificity phosphatase that preferentially dephosphorylates p38 MAPK and c-Jun N-terminal kinase (JNK), resulting in the attenuation of TLR-triggered production of proinflammatory cytokines. MKP-1 is posttranslationally modified by multiple mechanisms, including phosphorylation. A study now demonstrates that MKP-1 is also acetylated on a key lysine residue following stimulation of TLRs. Acetylation of MKP-1 promotes the interaction of MKP-1 with its substrate p38 MAPK, which results in dephosphorylation of p38 MAPK and the inhibition of innate immunity.
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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
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Lang R
DOI：
10.1084/jem.20071728
发表时间：
2008-06-09
期刊：
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影响因子：
--
作者：
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影响因子：
4.4
作者：
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影响因子：
11.4
作者：
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影响因子：
4
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