The JAK-STAT pathway: from structural biology to cytokine engineering.

IF 40.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
You Lv, Jianxun Qi, Jeffrey J Babon, Longxing Cao, Guohuang Fan, Jiajia Lang, Jin Zhang, Pengbing Mi, Bostjan Kobe, Faming Wang
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Abstract

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway serves as a paradigm for signal transduction from the extracellular environment to the nucleus. It plays a pivotal role in physiological functions, such as hematopoiesis, immune balance, tissue homeostasis, and surveillance against tumors. Dysregulation of this pathway may lead to various disease conditions such as immune deficiencies, autoimmune diseases, hematologic disorders, and cancer. Due to its critical role in maintaining human health and involvement in disease, extensive studies have been conducted on this pathway, ranging from basic research to medical applications. Advances in the structural biology of this pathway have enabled us to gain insights into how the signaling cascade operates at the molecular level, laying the groundwork for therapeutic development targeting this pathway. Various strategies have been developed to restore its normal function, with promising therapeutic potential. Enhanced comprehension of these molecular mechanisms, combined with advances in protein engineering methodologies, has allowed us to engineer cytokines with tailored properties for targeted therapeutic applications, thereby enhancing their efficiency and safety. In this review, we outline the structural basis that governs key nodes in this pathway, offering a comprehensive overview of the signal transduction process. Furthermore, we explore recent advances in cytokine engineering for therapeutic development in this pathway.

Abstract Image

JAK-STAT 通路:从结构生物学到细胞因子工程学。
Janus 激酶-信号转导和转录激活因子(JAK-STAT)途径是细胞外环境向细胞核进行信号转导的范例。它在造血、免疫平衡、组织稳态和肿瘤监控等生理功能中发挥着关键作用。这一途径的失调可能导致各种疾病,如免疫缺陷、自身免疫性疾病、血液病和癌症。由于该通路在维持人类健康和疾病中的关键作用,人们对其进行了从基础研究到医疗应用的广泛研究。这一通路的结构生物学研究取得了进展,使我们能够深入了解信号级联在分子水平上是如何运作的,从而为开发针对这一通路的疗法奠定了基础。目前已开发出各种策略来恢复其正常功能,治疗潜力巨大。对这些分子机制的深入理解,再加上蛋白质工程方法的进步,使我们能够为靶向治疗应用设计具有定制特性的细胞因子,从而提高其效率和安全性。在这篇综述中,我们将概述支配这一通路关键节点的结构基础,全面介绍信号转导过程。此外,我们还将探讨细胞因子工程学在该通路治疗开发方面的最新进展。
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来源期刊
Signal Transduction and Targeted Therapy
Signal Transduction and Targeted Therapy Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
44.50
自引率
1.50%
发文量
384
审稿时长
5 weeks
期刊介绍: Signal Transduction and Targeted Therapy is an open access journal that focuses on timely publication of cutting-edge discoveries and advancements in basic science and clinical research related to signal transduction and targeted therapy. Scope: The journal covers research on major human diseases, including, but not limited to: Cancer,Cardiovascular diseases,Autoimmune diseases,Nervous system diseases.
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