Institut für Biochemie und Molekularbiologie, RWTH Aachen University, Aachen, Germany.
Eur J Cell Biol. 2012 Jun-Jul;91(6-7):524-32. doi: 10.1016/j.ejcb.2011.09.005. Epub 2011 Oct 21.
The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway directly links ligand-binding to a membrane-bound receptor with the activation of a transcription factor. This signalling module enables the cell to rapidly initiate a transcriptional response to external stimulation. The main components of this evolutionary conserved module are cytokines that specifically bind to cytokine receptors leading to the activation of receptor-associated Janus tyrosine kinases (JAKs). The receptor-bound JAKs activate STAT transcription factors through phosphorylation of a single tyrosine residue. Activated STAT dimers translocate into the nucleus to induce target gene expression. In this article we will review current opinions on the molecular mechanism and on intracellular dynamics of JAK/STAT signalling with a special focus on the cytokine receptor glycoprotein 130 (gp130) and STAT3. In particular we will concentrate on non-canonical aspects of Jak/STAT signalling including preassembled receptor complexes, preformed STAT dimers, STAT trafficking and non-canonical functions of STATs.
Janus 激酶/信号转导子和转录激活子（JAK/STAT）通路将配体结合到细胞膜受体与转录因子的激活直接联系起来。这个信号模块使细胞能够迅速对外界刺激启动转录反应。这个进化上保守的模块的主要成分是细胞因子，它们特异性地结合细胞因子受体，导致受体相关的 Janus 酪氨酸激酶（JAK）的激活。受体结合的 JAK 通过磷酸化一个单一的酪氨酸残基来激活 STAT 转录因子。激活的 STAT 二聚体易位到细胞核中，诱导靶基因的表达。在本文中，我们将回顾 JAK/STAT 信号转导的分子机制和细胞内动力学的最新观点，特别关注细胞因子受体糖蛋白 130（gp130）和 STAT3。我们将特别关注 Jak/STAT 信号转导的非典型方面，包括预组装的受体复合物、预先形成的 STAT 二聚体、STAT 运输和 STAT 的非典型功能。
