Two-component signaling circuit structure and properties

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Various modeling and experimental studies have analyzed the reactions, interconnections, and motifs in two-component systems, with an eye toward understanding their physiological implications and the differences between alternative designs. Examples where recent progress has been made include aspects of autoregulation, signal integration in branched pathways, cross-talk suppression, and cross-regulation via connector proteins.

Introduction

Studies of two-component systems have revealed a diversity of designs that control the flow of information within and between circuits. Despite the variety and increasing complexity of these systems, some aspects are amenable to simple modeling. This type of analysis, when closely coupled with experiments, bolsters one's intuition, gives insights into the functioning of these circuits, and provides a starting point for analyzing the larger networks within which two-component systems are embedded. This review will cover some of the simple design features that are commonly found in two-component systems and that have been explored through modeling and experiment. The emphasis will not be on the methods for modeling regulatory circuits but rather on the conclusions reached as a result of modeling.

Section snippets

Single-step phosphotransfer

The pathways of phosphorylation and dephosphorylation are at the heart of two-component signaling. In some circuits, the histidine kinase plays a role only in response regulator phosphorylation. The best-studied example is the histidine kinase CheA in chemotaxis circuits, where response regulator dephosphorylation is controlled by a separate phosphatase (see [1] for a recent review). In many two-component systems, however, the histidine kinase participates in the phosphorylation and

Branched pathways

In some two-component systems, the phosphorylation pathway is branched, with more than one source or target of phosphotransfer [36], Figure 1a, b. Such branched pathways can either be many-to-one, in which multiple phosphodonors phosphorylate a single protein, or ‘one-to-many’ in which the phosphodonor phosphorylates multiple targets. A well-studied example of ‘one-to-many’ branched regulation is found in bacterial chemotaxis, where the histidine kinase CheA phosphorylates the two response

Concluding remarks

Studies of phosphotransfer-based signaling circuits continue to reveal new layers of complexity for these systems. Indeed, there are fewer and fewer examples of signal transduction pathways that really are made up of only ‘two components’. To provide some level of organization and understanding for this subject, there is a growing need to characterize the properties of different circuit architectures and, wherever possible, the general principles that govern their function, through modeling and

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

The research from the Goulian lab that was covered in this review was supported by grants from the National Science Foundation and National Institutes of Health.

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