Kumar Rakesh, Sanawar Rahul, Li Xiaodong, Li Feng
Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA; Cancer Biology Program, Rajiv Gandhi Center of Biotechnology, Thiruvananthapuram 695014, India.
Cancer Biology Program, Rajiv Gandhi Center of Biotechnology, Thiruvananthapuram 695014, India.
Gene. 2017 Mar 20;605:20-31. doi: 10.1016/j.gene.2016.12.014. Epub 2016 Dec 19.
PAKs, p21-activated kinases, play central roles and act as converging junctions for discrete signals elicited on the cell surface and for a number of intracellular signaling cascades. PAKs phosphorylate a vast number of substrates and act by remodeling cytoskeleton, employing scaffolding, and relocating to distinct subcellular compartments. PAKs affect wide range of processes that are crucial to the cell from regulation of cell motility, survival, redox, metabolism, cell cycle, proliferation, transformation, stress, inflammation, to gene expression. Understandably, their dysregulation disrupts cellular homeostasis and severely impacts key cell functions, and many of those are implicated in a number of human diseases including cancers, neurological disorders, and cardiac disorders. Here we provide an overview of the members of the PAK family and their current status. We give special emphasis to PAK1 and PAK4, the prototypes of groups I and II, for their profound roles in cancer, the nervous system, and the heart. We also highlight other family members. We provide our perspective on the current advancements, their growing importance as strategic therapeutic targets, and our vision on the future of PAKs.
p21激活激酶（PAKs）发挥着核心作用，是细胞表面引发的离散信号以及众多细胞内信号级联反应的汇聚节点。PAKs可磷酸化大量底物，通过重塑细胞骨架、利用支架作用以及重新定位到不同的亚细胞区室来发挥作用。PAKs影响着对细胞至关重要的广泛过程，从细胞运动、存活、氧化还原、代谢、细胞周期、增殖、转化、应激、炎症到基因表达。可以理解的是，它们的失调会破坏细胞内稳态并严重影响关键细胞功能，其中许多功能与包括癌症、神经疾病和心脏疾病在内的多种人类疾病有关。在此，我们概述PAK家族成员及其当前状况。我们特别强调I组和II组的原型PAK1和PAK4，因为它们在癌症、神经系统和心脏中具有重要作用。我们还突出了其他家族成员。我们阐述了对当前进展的看法、它们作为战略治疗靶点日益增长的重要性以及我们对PAKs未来的展望。
