Liu Hui, Liu Kangdong, Dong Zigang
Department of Pathophysiology, School of Basic Medical Sciences, The Academy of Medical Science, College of Medical, Zhengzhou University, Zhengzhou, China.
China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.
Front Cell Dev Biol. 2021 Mar 16;9:641381. doi: 10.3389/fcell.2021.641381. eCollection 2021.
The p21-activated kinases (PAKs), downstream effectors of Ras-related Rho GTPase Cdc42 and Rac, are serine/threonine kinases. Biologically, PAKs participate in various cellular processes, including growth, apoptosis, mitosis, immune response, motility, inflammation, and gene expression, making PAKs the nexus of several pathogenic and oncogenic signaling pathways. PAKs were proved to play critical roles in human diseases, including cancer, infectious diseases, neurological disorders, diabetes, pancreatic acinar diseases, and cardiac disorders. In this review, we systematically discuss the structure, function, alteration, and molecular mechanisms of PAKs that are involved in the pathogenic and oncogenic effects, as well as PAK inhibitors, which may be developed and deployed in cancer therapy, anti-viral infection, and other diseases. Furthermore, we highlight the critical questions of PAKs in future research, which provide an opportunity to offer input and guidance on new directions for PAKs in pathogenic, oncogenic, and drug discovery research.
p21激活激酶（PAKs）是Ras相关的Rho GTP酶Cdc42和Rac的下游效应器，属于丝氨酸/苏氨酸激酶。在生物学上，PAKs参与多种细胞过程，包括生长、凋亡、有丝分裂、免疫反应、运动、炎症和基因表达，这使得PAKs成为多种致病和致癌信号通路的枢纽。事实证明，PAKs在人类疾病中发挥着关键作用，这些疾病包括癌症、传染病、神经疾病、糖尿病、胰腺腺泡疾病和心脏疾病。在本综述中，我们系统地讨论了PAKs的结构、功能、改变及其参与致病和致癌作用的分子机制，以及可能用于癌症治疗、抗病毒感染和其他疾病的PAK抑制剂。此外，我们强调了PAKs在未来研究中的关键问题，这为在致病、致癌和药物发现研究中为PAKs的新方向提供意见和指导提供了机会。
