Multikinase Networks: Two-Component Signaling Networks Integrating Multiple Stimuli

Bacteria depend on two-component systems (TCSs) to detect and respond to threats. Simple pathways comprise a single sensor kinase (SK) that detects a signal and activates a response regulator (RR) protein to mediate an appropriate output. These simple pathways with only a single SK are not that well suited to making complex decisions where multiple different stimuli need to be evaluated. A recently emerging theme is the existence of multikinase-networks (MKNs) where multiple SKs collaborate to detect and integrate numerous different signals to regulate a major lifestyle switch e.g. virulence, sporulation, biofilm formation and cell division. In this review, the role of MKNs and the phosphosignalling mechanisms underpinning their signal integration and decision making will be explored.