Analysis of network motifs in cellular regulation: Structural similarities, input–output relations and signal integration

Abstract

Much of the complexity of regulatory networks derives from the necessity to integrate multiple signals and to avoid malfunction due to cross-talk or harmful perturbations. Hence, one may expect that the input-output behavior of larger networks is not necessarily more complex than that of smaller network motifs which suggests that both can, under certain conditions, be described by similar equations. In this review, we illustrate this approach by discussing the similarities that exist in the steady state descriptions of a simple bimolecular reaction, covalent modification cycles and bacterial two-component systems. Interestingly, in all three systems fundamental input-output characteristics such as thresholds, ultrasensitivity or concentration robustness are described by structurally similar equations. Depending on the system the meaning of the parameters can differ ranging from protein concentrations and affinity constants to complex parameter combinations which allows for a quantitative understanding of signal integration in these systems. We argue that this approach may also be extended to larger regulatory networks.

Overview of protein phosphorylation in bacteria with a main focus on unusual protein kinases in Bacillus subtilis

“…Despite that the sensor kinases are highly specific of their cognate response regulators, several crosstalks between TCSs have been reported; they may be due to the co-evolution of the participating proteins [16,17]. Although this phosphorelay system is qualified to be bacterial since TCSs are present in a wide range of bacterial species and regulate a variety of cellular processes [18], they seem also present in lower eukaryotes [19,20].…”

The Hitchhiker’s Guide to Organophosphate Chemistry

“…Some of the kinases have both a kinase and a phosphatase domain, which has important implications in cellular signaling. [24][25][26] How inositol pyrophosphates control different cellular and organismal processes is currently under investigation by several groups. Since they contain an energy-rich phosphoanhydride bond, they can in principle signal by three distinct mechanisms: 1) by receptor binding, 2) by phosphate transfer, and 3) by event timing.…”

Biochemical network motifs can transduce and process oscillatory information

“…6 It has been well established that adapter proteins and enzymes responsible for processing biological signals can be modelled in subgraphs known as network motifs. 7,8 Two-, three-and four-node network motifs are most commonly studied, as well as most ubiquitously present in nature. 9,10 Although these simple motifs can form large networks that can carry out highly complex decision-making processes, 11 even the simplest forms, such as a two-node positive feedback loop, could result in complex phenomena, such as bi-stability.…”