Histidine kinases and response regulators in networks

Two-component systems, composed of a histidine kinase (HK) and a response regulator (RR), are the major signal transduction devices in bacteria. Originally it was thought that these two components function as linear, phosphorylation-driven stimulus–response system. Here, we will review how accessory proteins are employed by HKs and RRs to mediate signal integration, scaffolding, interconnection and allosteric regulation, and how these two components are embedded in regulatory networks.

► Histidine kinase/response regulator systems are important signaling devices.
► Various accessory proteins are involved in co-sensing and signal integration.
► Scaffold proteins assemble histidine kinase/response regulator pathways.
► Histidine kinases and response regulators are embedded in networks.