Regulation of JNK and p38 MAPK in the immune system: signal integration, propagation and termination.

Regulation of JNK and p38 MAPK in the immune system: signal integration, propagation and termination.
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DOI:
10.1016/j.cyto.2009.08.002
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发表时间:
2009-12
期刊:
影响因子:
3.8
通讯作者:
Chi, Hongbo
Chi, Hongbo
中科院分区:
医学3区
文献类型:
--
作者:
Huang, Gonghua;Shi, Lewis Zhichang;Chi, Hongbo

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由JNK和p38组成的应激激活的MAP激酶(MAPKs)在先天性和适应性免疫系统中发挥重要作用。MAPK的激活由三层激酶模块介导,该三层激酶模块包括MAPK激酶激酶(MAP3Ks)、MAPK激酶(MAP2Ks)和MAPK,通过顺序的蛋白磷酸化。活化的MAPK反过来磷酸化转录因子和其他靶点以调节基因转录和免疫应答。最近的研究为MAPK通路的上游和下游组分提供了新的见解,这些组分促进了免疫应答中MAPK信号的激活和传播。此外,MAPK活性受MAPK磷酸酶(MKPs)负调控,MAPK磷酸酶是一组使MAPK去磷酸化和磷酸化的双特异性磷酸酶。在这里,我们讨论了我们对MAPK信号转导中这些调节过程的理解的最新进展,重点是它们对免疫功能的影响。
Stress-activated MAP kinases (MAPKs), comprised of JNK and p38, play prominent roles in the innate and adaptive immune systems. Activation of MAPKs is mediated by a three-tiered kinase module comprised of MAPK kinase kinases (MAP3Ks), MAPK kinases (MAP2Ks) and MAPKs through sequential protein phosphorylation. Activated MAPKs, in turn, phosphorylate transcription factors and other targets to regulate gene transcription and immune responses. Recent studies have provided new insight into the upstream and downstream components of the MAPK pathway that facilitate the activation and propagation of MAPK signaling in immune responses. Moreover, MAPK activity is negatively regulated by MAPK phosphatases (MKPs), a group of dual-specificity phosphatases that dephosphorylate and inactivate the MAPKs. Here we discuss the recent advances in our understanding of these regulatory processes in MAPK signaling with a focus on their impacts on immune function.
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