Brierley Melissa M, Fish Eleanor N
Division of Cell & Molecular Biology, Toronto General Research Institute, University Health Network, University of Toronto, Toronto, Ontario M5G 2M1, Canada.
J Interferon Cytokine Res. 2005 Dec;25(12):733-44. doi: 10.1089/jir.2005.25.733.
The high-affinity binding interactions between interferons (IFNs) and their cognate cell surface receptors lead to the activation of receptor-associated Janus protein tyrosine kinases (Jaks) and subsequent phosphorylation and activation of a group of transcription factors, the signal transducers and activators of transcription (Stats). Upon IFN-induced activation, these Stat proteins form homodimeric and heterodimeric complexes that translocate to the nucleus and bind specific elements within the promoters of IFN-stimulated genes (ISGs). In addition to the well-studied IFN-induced ISG factor 3 (ISGF3) and Stat1:1 complexes, IFNs induce the formation of a number of other Stat-containing complexes, including Stat3:3 and Stat5:5 homodimers, as well as Stat2:1 and Stat5:CrkL heterodimers, that also mediate gene transcription. Moreover, emerging evidence suggests that particular amino acid residues within the individual Stat proteins contribute to different aspects of Stat function. These residues modulate the transcriptional activation potential of Stat-containing complexes and thereby influence the expression of ISGs. Indeed, the Stat proteins function in a multifaceted manner to regulate the expression of proteins that mediate IFN responses.
干扰素（IFN）与其同源细胞表面受体之间的高亲和力结合相互作用导致受体相关的Janus蛋白酪氨酸激酶（Jaks）激活，随后一组转录因子即信号转导子和转录激活子（Stats）发生磷酸化并被激活。在IFN诱导激活后，这些Stat蛋白形成同二聚体和异二聚体复合物，它们转位至细胞核并结合IFN刺激基因（ISG）启动子内的特定元件。除了研究充分的IFN诱导的ISG因子3（ISGF3）和Stat1:1复合物外，IFN还诱导形成许多其他含Stat的复合物，包括Stat3:3和Stat5:5同二聚体，以及Stat2:1和Stat5:CrkL异二聚体，它们也介导基因转录。此外，新出现的证据表明，单个Stat蛋白内的特定氨基酸残基对Stat功能的不同方面有贡献。这些残基调节含Stat复合物的转录激活潜能，从而影响ISG的表达。实际上，Stat蛋白以多方面的方式发挥作用，以调节介导IFN反应的蛋白质的表达。
