Untangling the complexity of PAK1 dynamics: The future challenge

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.