Kisseleva T, Bhattacharya S, Braunstein J, Schindler C W
Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Gene. 2002 Feb 20;285(1-2):1-24. doi: 10.1016/s0378-1119(02)00398-0.
Investigation into the mechanism of cytokine signaling led to the discovery of the JAK/STAT pathway. Following the binding of cytokines to their cognate receptor, signal transducers and activators of transcription (STATs) are activated by members of the janus activated kinase (JAK) family of tyrosine kinases. Once activated, they dimerize and translocate to the nucleus and modulate the expression of target genes. During the past several years significant progress has been made in the characterization of the JAK/STAT signaling cascade, including the identification of multiple STATs and regulatory proteins. Seven STATs have been identified in mammals. The vital role these STATs play in the biological response to cytokines has been demonstrated through the generation of murine 'knockout' models. These mice will be invaluable in carefully elucidating the role STATs play in regulating the host response to various stresses. Similarly, the solution of the crystal structure of two STATs has and will continue to facilitate our understanding of how STATs function. This review will highlight these exciting developments in JAK/STAT signaling.
对细胞因子信号传导机制的研究导致了JAK/STAT途径的发现。细胞因子与其同源受体结合后，信号转导子和转录激活子（STATs）被酪氨酸激酶的janus激活激酶（JAK）家族成员激活。一旦被激活，它们就会二聚化并转移到细胞核中，调节靶基因的表达。在过去的几年里，在JAK/STAT信号级联的表征方面取得了重大进展，包括多种STATs和调节蛋白的鉴定。在哺乳动物中已鉴定出七种STATs。通过生成小鼠“敲除”模型，已证明这些STATs在对细胞因子的生物学反应中所起的重要作用。这些小鼠对于仔细阐明STATs在调节宿主对各种应激的反应中所起的作用将是非常宝贵的。同样，两种STATs晶体结构的解析已经并将继续促进我们对STATs功能的理解。本综述将重点介绍JAK/STAT信号传导中这些令人兴奋的进展。
