What do archaeal and eukaryotic histidine kinases sense?

Signal transduction systems configured around a core phosphotransfer step between a histidine kinase and a cognate response regulator protein occur in organisms from all domains of life. These systems, termed two-component systems, constitute the majority of multi-component signaling pathways in Bacteria but are less prevalent in Archaea and Eukarya. The core signaling domains are modular, allowing versatility in configuration of components into single-step phosphotransfer and multi-step phosphorelay pathways, the former being predominant in bacteria and the latter in eukaryotes. Two-component systems regulate key cellular regulatory processes that provide adaptive responses to environmental stimuli and are of interest for the development of antimicrobial therapeutics, biotechnology applications, and biosensor engineering. In bacteria, two-component systems have been found to mediate responses to an extremely broad array of extracellular and intracellular chemical and physical stimuli, whereas in archaea and eukaryotes, the use of two-component systems is more limited. This review summarizes recent advances in exploring the repertoire of sensor histidine kinases in the Archaea and Eukarya domains of life.