Structure, biochemistry, and biology of PAK kinases.
Structure, biochemistry, and biology of PAK kinases.
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PAK 激酶的结构、生物化学和生物学
DOI：
10.1016/j.gene.2016.12.014
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发表时间：
2017-03-20
期刊：
影响因子：
3.5
通讯作者：
Li F
中科院分区：
文献类型：
--
作者：
Kumar R;Sanawar R;Li X;Li F
PAK是p21激活的蛋白激酶，在细胞表面引发的离散信号和许多细胞内信号级联中起着中心作用和汇聚连接的作用。PAK使大量底物磷酸化，并通过重塑细胞骨架、使用支架和重新定位到不同的亚细胞隔间来发挥作用。PAK对细胞的运动、存活、氧化还原、新陈代谢、细胞周期、增殖、转化、应激、炎症、基因表达等多种过程起着至关重要的调节作用。可以理解的是，它们的调节失调扰乱了细胞的动态平衡，严重影响了关键细胞功能，其中许多与许多人类疾病有关，包括癌症、神经疾病和心脏疾病。在这里，我们概述PAK大家庭的成员及其现状。我们特别强调PAK1和PAK4，它们是第一组和第二组的原型，因为它们在癌症、神经系统和心脏中发挥着深远的作用。我们还会突出显示其他家庭成员。我们提供了我们对当前进展的看法，它们作为战略治疗目标的日益重要，以及我们对PAK的未来的展望。
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.