Numb相关激酶的生理功能及其在病毒感染中的作用

Numb-associated kinases: physiological functions and roles in viral infection

摘要:

Numb相关激酶(Numb-associated kinases, NAKs)家族是一类在进化上高度保守的丝氨酸/苏氨酸蛋白激酶，由衔接蛋白相关激酶1 (adaptor-associated kinase 1, AAK1)、细胞周期蛋白G相关激酶(cyclin G-associated kinase, GAK)、骨形态发生蛋白2诱导激酶(bone morphogenetic protein 2-inducible kinase, BMP2K)和丝氨酸/苏氨酸激酶16 (serine/threonine kinase 16, STK16)这4个成员构成。NAKs广泛参与调控细胞的内吞、胞内运输、分化、自噬以及信号转导等基本生命活动。近年来，研究发现NAKs在多种病毒生命周期的不同阶段，包括入侵、组装、释放以及免疫逃逸等环节均发挥着关键作用。同时，已有针对NAKs的小分子抑制剂应用于相关生理性或病毒感染性疾病的临床研究与治疗。本文将系统梳理NAKs的主要生理功能及其在病毒感染中的作用，为病毒致病机制研究和以NAKs为靶点的新药开发提供参考依据。

Abstract:

Numb-associated kinases (NAKs) are a family of evolutionarily conserved serine/threonine kinases, encompassing adaptor-associated kinase 1 (AAK1), cyclin G-associated kinase (GAK), bone morphogenetic protein 2-inducible kinase (BMP2K), and serine/threonine kinase 16 (STK16). NAKs are widely involved in various physiological processes, such as endocytosis, intracellular transport, cell differentiation, autophagy, and signal transduction. In recent years, studies have shown that NAKs play a key role in different life cycle stages including virus entry, assembly, release, and immune escape of various viruses. Furthermore, small-molecule inhibitors targeting NAKs have been applied in clinical research and treatment of related physiological or viral infectious diseases. This article systematically reviews the primary physiological functions of NAKs and their roles in viral infection, aiming to provide a theoretical foundation for elucidating the pathogenic mechanisms of viruses and developing novel therapeutic drugs targeting NAKs.