Response Regulator Proteins and Their Interactions with Histidine Protein Kinases

Response regulator proteins function together with histidine protein kinases in two-component signal transduction pathways. Response regulators are typically composed of a conserved regulatory domain that controls the activity of a variable effector domain that mediates the specific output response. The conserved regulatory domain functions as a phosphorylation-regulated switch. Aside from the intrinsic autophosphatase activity of response regulators and/or the activity of auxiliary phosphatases, the major locus for the regulation of response regulator phosphorylation is the histidine kinase. Histidine kinases provide the phosphoryl groups for phosphotransfer reactions catalyzed by response regulators. In some systems, the autophosphorylation rate of the histidine kinase determines the level of response regulator phosphorylation. In other systems, the level of response regulator phosphorylation is controlled by a response regulator phosphatase activity of the histidine kinase.. The interaction of RRs with His-containing domains presumably occurs only transiently during the phosphotransfer reaction. The phosphorylated RR is then be expected to dissociate and interact with other downstream effectors, as observed with phospho-CheY.