Ultrasensitive response motifs: Basic amplifiers in molecular signalling networks

Center for Dose Response Modeling, Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA.
Open Biology (Impact Factor: 5.78). 04/2013; 3(4):130031. DOI: 10.1098/rsob.130031
Source: PubMed


Multi-component signal transduction pathways and gene regulatory circuits underpin integrated cellular responses to perturbations. A recurring set of network motifs serve as the basic building blocks of these molecular signalling networks. This review focuses on ultrasensitive response motifs (URMs) that amplify small percentage changes in the input signal into larger percentage changes in the output response. URMs generally possess a sigmoid input-output relationship that is steeper than the Michaelis-Menten type of response and is often approximated by the Hill function. Six types of URMs can be commonly found in intracellular molecular networks and each has a distinct kinetic mechanism for signal amplification. These URMs are: (i) positive cooperative binding, (ii) homo-multimerization, (iii) multistep signalling, (iv) molecular titration, (v) zero-order covalent modification cycle and (vi) positive feedback. Multiple URMs can be combined to generate highly switch-like responses. Serving as basic signal amplifiers, these URMs are essential for molecular circuits to produce complex nonlinear dynamics, including multistability, robust adaptation and oscillation. These dynamic properties are in turn responsible for higher-level cellular behaviours, such as cell fate determination, homeostasis and biological rhythm.

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Available from: Melvin Andersen, Apr 21, 2014
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    • "Curiously, a minimum threshold quantity of S-RNase in the style is required to trigger the self-incompatibility reaction [30], [32], [51], but to date, no mechanism has yet been proposed to account for this. The threshold phenomenon is conceptually akin to a sigmoidal or ultrasensitive response for which a variety of mechanisms, including co-operativity, positive feedback loops and molecular titration [52] have been proposed. It is an intriguing possibility that eEF1A may potentially act to titrate the amount of free S-RNase following import into the pollen tube cytoplasm. "
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