Department of Cancer Biology, Lerner Research Institute of the Cleveland Clinic, Cleveland, Ohio 44195.
Cold Spring Harb Perspect Biol. 2018 Jan 2;10(1):a028555. doi: 10.1101/cshperspect.a028555.
Many cytokines and all interferons activate members of a small family of kinases (the Janus kinases [JAKs]) and a slightly larger family of transcription factors (the signal transducers and activators of transcription [STATs]), which are essential components of pathways that induce the expression of specific sets of genes in susceptible cells. JAK-STAT pathways are required for many innate and acquired immune responses, and the activities of these pathways must be finely regulated to avoid major immune dysfunctions. Regulation is achieved through mechanisms that include the activation or induction of potent negative regulatory proteins, posttranslational modification of the STATs, and other modulatory effects that are cell-type specific. Mutations of JAKs and STATs can result in gains or losses of function and can predispose affected individuals to autoimmune disease, susceptibility to a variety of infections, or cancer. Here we review recent developments in the biochemistry, genetics, and biology of JAKs and STATs.
许多细胞因子和所有干扰素激活一小族激酶（Janus 激酶[JAK]）和稍大一些的转录因子家族（信号转导子和转录激活子[STAT]）的成员，这些激酶和转录因子是诱导易感细胞中特定基因表达的途径的重要组成部分。JAK-STAT 途径是许多先天和获得性免疫反应所必需的，这些途径的活性必须精细调节以避免主要的免疫功能障碍。调节是通过包括激活或诱导强效负调节蛋白、STAT 的翻译后修饰以及其他具有细胞类型特异性的调节作用的机制来实现的。JAK 和 STAT 的突变可导致功能的获得或丧失，并可使受影响的个体易患自身免疫性疾病、易受各种感染或癌症的影响。在这里，我们综述了 JAK 和 STAT 的生物化学、遗传学和生物学的最新进展。
