Cross-talk and specificity in two-component signal transduction pathways

Two-component signaling systems (TCSs) are composed of two proteins, sensor kinases and response regulators, which can cross-talk and integrate information between them by virtue of high-sequence conservation and modular nature, to generate concerted and diversified responses. However, TCSs have been shown to be insulated, to facilitate linear signal transmission and response generation. Here, we discuss various mechanisms that confer specificity or cross-talk among TCSs. The presented models are supported with evidence that indicate the physiological significance of the observed TCS signaling architecture. Overall, we propose that the signaling topology of any TCSs cannot be predicted using obvious sequence or structural rules, as TCS signaling is regulated by multiple factors, including spatial and temporal distribution of the participating proteins