The JAK-STAT pathway at twenty.

The JAK-STAT pathway at twenty.
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DOI:
10.1016/j.immuni.2012.03.013
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发表时间:
2012-04-20
期刊:
影响因子:
32.4
通讯作者:
Darnell JE Jr
Darnell JE Jr
中科院分区:
医学1区
文献类型:
--
作者:
Stark GR;Darnell JE Jr

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我们回顾了酪氨酸激酶TYK2和JAK1以及转录因子STAT1、STAT2和IRF9在细胞对I型干扰素的反应中所需的发现。对JAK-STAT通路的这一初步描述很快导致了更多的发现,即II型干扰素和许多其他细胞因子通过类似的机制发出信号。这一众所周知的途径现在是一个范例,展示了来自细胞表面蛋白质-蛋白质接触的信息如何直接传递到细胞核中的基因。我们还回顾了最近关于STAT蛋白的工作,这些工作显示了几种不同的翻译后修饰的重要性,包括丝氨酸磷酸化、乙酰化、甲基化和总甲基化。这些非常熟练的蛋白质还在转录调控中提供非规范功能,它们还以可能根本不涉及转录的方式在线粒体呼吸和染色质组织中发挥作用。
We look back on the discoveries that the tyrosine kinases TYK2 and JAK1 and the transcription factors STAT1, STAT2, and IRF9 are required for the cellular response to type I interferons. This initial description of the JAK-STAT pathway led quickly to additional discoveries that type II interferons and many other cytokines signal through similar mechanisms. This well-understood pathway now serves as a paradigm showing how information from protein-protein contacts at the cell surface can be conveyed directly to genes in the nucleus. We also review recent work on the STAT proteins showing the importance of several different posttranslational modifications, including serine phosphorylation, acetylation, methylation, and sumoylation. These remarkably proficient proteins also provide noncanonical functions in transcriptional regulation and they also function in mitochondrial respiration and chromatin organization in ways that may not involve transcription at all.
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