Liongue Clifford, Ratnayake Tarindhi, Basheer Faiza, Ward Alister C
School of Medicine, Deakin University, Geelong, VIC 3216, Australia.
The Institute for Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, Geelong, VIC 3216, Australia.
Int J Mol Sci. 2024 Mar 4;25(5):2977. doi: 10.3390/ijms25052977.
The Janus kinase (JAK) family is a small group of protein tyrosine kinases that represent a central component of intracellular signaling downstream from a myriad of cytokine receptors. The JAK3 family member performs a particularly important role in facilitating signal transduction for a key set of cytokine receptors that are essential for immune cell development and function. Mutations that impact JAK3 activity have been identified in a number of human diseases, including somatic gain-of-function (GOF) mutations associated with immune cell malignancies and germline loss-of-function (LOF) mutations associated with immunodeficiency. The structure, function and impacts of both GOF and LOF mutations of JAK3 are highly conserved, making animal models highly informative. This review details the biology of JAK3 and the impact of its perturbation in immune cell-related diseases, including relevant animal studies.
Janus激酶（JAK）家族是一小类蛋白质酪氨酸激酶，是众多细胞因子受体下游细胞内信号传导的核心组成部分。JAK3家族成员在促进一组对免疫细胞发育和功能至关重要的关键细胞因子受体的信号转导中发挥着特别重要的作用。在许多人类疾病中已发现影响JAK3活性的突变，包括与免疫细胞恶性肿瘤相关的体细胞功能获得性（GOF）突变和与免疫缺陷相关的种系功能丧失性（LOF）突变。JAK3的GOF和LOF突变的结构、功能及影响高度保守，使得动物模型具有很高的参考价值。本文综述详细介绍了JAK3的生物学特性及其在免疫细胞相关疾病中的干扰影响，包括相关的动物研究。
