c-Jun N-Terminal Kinase: A Spatiotemporal Regulator of Cell Fate and Function

c-Jun N-terminal kinase (JNK) is a highly conserved, stress-activated protein kinase that plays key roles in cellular development and cell fate. An extensive study over more than 30 years has identified roughly 100 substrates for this kinase including the transcription factor c-Jun and other cell fate effectors. These studies have shown that JNK activation is tightly regulated both spatially through recruitment to subcellular locations and temporally through specific activation dynamics. Ultimately, these two regulatory mechanisms contribute to JNK’s function as a major driver of cell fate and function. A growing field of live-cell imaging, biosensor development, and other novel approaches to manipulate kinase function and localization are now providing novel insights into JNK function at the single-cell level. The purpose of this review is to illustrate our historical understanding of the spatiotemporal functions of JNK signaling within cells as well as emerging studies within the field. Ultimately, we aim to provide insight into remaining knowledge gaps within the field and how emerging technologies may help address these questions.