College of Pharmacy, Harbin Medical University-Daqing, Daqing 163319, China.
Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
Int Immunopharmacol. 2020 Mar;80:106210. doi: 10.1016/j.intimp.2020.106210. Epub 2020 Jan 20.
The JAK/STAT signaling pathway is an universally expressed intracellular signal transduction pathway and involved in many crucial biological processes, including cell proliferation, differentiation, apoptosis, and immune regulation. It provides a direct mechanism for extracellular factors-regulated gene expression. Current researches on this pathway have been focusing on the inflammatory and neoplastic diseases and related drug. The mechanism of JAK/STAT signaling is relatively simple. However, the biological consequences of the pathway are complicated due to its crosstalk with other signaling pathways. In addition, there is increasing evidence indicates that the persistent activation of JAK/STAT signaling pathway is closely related to many immune and inflammatory diseases, yet the specific mechanism remains unclear. Therefore, it is necessary to study the detailed mechanisms of JAK/STAT signaling in disease formation to provide critical reference for clinical treatments of the diseases. In this review, we focus on the structure of JAKs and STATs, the JAK/STAT signaling pathway and its negative regulators, the associated diseases, and the JAK inhibitors for the clinical therapy.
JAK/STAT 信号通路是一种普遍表达的细胞内信号转导通路，参与许多关键的生物学过程，包括细胞增殖、分化、凋亡和免疫调节。它为细胞外因子调节基因表达提供了直接的机制。目前对该通路的研究主要集中在炎症和肿瘤性疾病及其相关药物上。JAK/STAT 信号通路的机制相对简单。然而，由于其与其他信号通路的串扰，该通路的生物学后果较为复杂。此外，越来越多的证据表明，JAK/STAT 信号通路的持续激活与许多免疫和炎症性疾病密切相关，但具体机制尚不清楚。因此，有必要研究 JAK/STAT 信号在疾病形成中的详细机制，为疾病的临床治疗提供重要参考。在这篇综述中，我们重点介绍 JAKs 和 STATs 的结构、JAK/STAT 信号通路及其负调节剂、相关疾病以及用于临床治疗的 JAK 抑制剂。
