Taglieri Domenico M, Ushio-Fukai Masuko, Monasky Michelle M
Department of Anesthesia and General Intensive Care Unit, Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 (Milano), Italy.
Department of Pharmacology, Center for Lung and Vascular Biology, Center for Cardiovascular Research, University of Illinois at Chicago, 835 S. Wolcott Ave. E403 MSB, M/C868, Chicago, IL 60612, USA.
Cell Signal. 2014 Sep;26(9):2060-9. doi: 10.1016/j.cellsig.2014.04.020. Epub 2014 May 2.
P-21 activated kinases, or PAKs, are serine-threonine kinases that serve a role in diverse biological functions and organ system diseases. Although PAK signaling has been the focus of many investigations, still our understanding of the role of PAK in inflammation is incomplete. This review consolidates what is known about PAK1 across several cell types, highlighting the role of PAK1 and PAK2 in inflammation in relation to NADPH oxidase activation. This review explores the physiological functions of PAK during inflammation, the role of PAK in several organ diseases with an emphasis on cardiovascular disease, and the PAK signaling pathway, including activators and targets of PAK. Also, we discuss PAK1 as a pharmacological anti-inflammatory target, explore the potentials and the limitations of the current pharmacological tools to regulate PAK1 activity during inflammation, and provide indications for future research. We conclude that a vast amount of evidence supports the idea that PAK is a central molecule in inflammatory signaling, thus making PAK1 itself a promising prospective pharmacological target.
p21激活激酶（PAKs）是丝氨酸 - 苏氨酸激酶，在多种生物学功能和器官系统疾病中发挥作用。尽管PAK信号传导一直是许多研究的重点，但我们对PAK在炎症中的作用的理解仍不完整。本综述整合了几种细胞类型中关于PAK1的已知信息，强调了PAK1和PAK2在与NADPH氧化酶激活相关的炎症中的作用。本综述探讨了PAK在炎症期间的生理功能、PAK在几种器官疾病（重点是心血管疾病）中的作用以及PAK信号通路，包括PAK的激活剂和靶点。此外，我们讨论了PAK1作为一种药理学抗炎靶点，探讨了当前药理学工具在炎症期间调节PAK1活性的潜力和局限性，并为未来研究提供了方向。我们得出结论，大量证据支持PAK是炎症信号传导中的核心分子这一观点，因此PAK1本身是一个有前景的潜在药理学靶点。
