p21激活的激酶(PAKs),Ras相关RhoGTPaseCdc42和Rac的下游效应子,是丝氨酸/苏氨酸激酶。生物学,PAK参与各种细胞过程,包括增长,凋亡,有丝分裂,免疫反应,运动性,炎症,和基因表达,使PAKs成为几种致病和致癌信号通路的纽带。PAK被证明在人类疾病中起关键作用,包括癌症,传染病,神经系统疾病,糖尿病,胰腺腺泡疾病,和心脏疾病。在这次审查中,我们系统地讨论了结构,函数,alteration,以及参与致病和致癌作用的PAKs的分子机制,以及PAK抑制剂,可以在癌症治疗中开发和部署,抗病毒感染,和其他疾病。此外,我们在未来的研究中强调了PAK的关键问题,这提供了一个机会,为致病性PAK的新方向提供投入和指导,致癌,和药物发现研究。
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.