Parrini Maria Carla
Institut Curie; Centre de Recherche; Paris, France; Inserm U830; Paris, France.
Cell Logist. 2012 Apr 1;2(2):78-83. doi: 10.4161/cl.19817.
PAK1 kinase is a crucial regulator of a variety of cellular processes, such as motility, cell division, gene transcription and apoptosis. Its deregulation is involved in several pathologies, including cancer, viral infection and neurodegenerative diseases. Due to this strong implication in human health, the complex network of signaling pathways centered on PAK1 is a subject of intensive investigations. This review summarizes the present knowledge on the multiple PAK1 intracellular localizations and on its shuttling between different compartments. The dynamics of PAK1 localization and activation are finely tuned by the cell and it is this tight control that underlies the capacity of PAK1 to participate in the regulation of many fundamental cell functions. Recently, PAK1 biosensors have been developed to visualize PAK1 activation in live cells. These new imaging tools should be of great help to better understand PAK1 biology and to conceive strategies for efficient and specific PAK1 inhibitors.
PAK1激酶是多种细胞过程的关键调节因子，如运动性、细胞分裂、基因转录和细胞凋亡。其失调涉及多种病理状况，包括癌症、病毒感染和神经退行性疾病。由于其对人类健康有如此重大的影响，以PAK1为中心的复杂信号通路网络成为了深入研究的对象。本综述总结了目前关于PAK1在细胞内多种定位及其在不同区室之间穿梭的知识。PAK1定位和激活的动态过程受到细胞的精细调控，正是这种严格的控制使得PAK1能够参与许多基本细胞功能的调节。最近，已经开发出PAK1生物传感器来可视化活细胞中PAK1的激活。这些新的成像工具将极大地有助于更好地理解PAK1生物学，并构思出有效且特异的PAK1抑制剂策略。
