Ultrasensitive response motifs: Basic amplifiers in molecular signalling networks

Qiang Zhang, Sudin Bhattacharya, Melvin E. Andersen

Research output: Research - peer-reviewArticle

  • 65 Citations

Abstract

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.

LanguageEnglish (US)
Article number130031
JournalOpen Biology
Volume3
Issue numberAPR
DOIs
StatePublished - 2013
Externally publishedYes

Profile

Nonlinear Dynamics
Gene Regulatory Networks
Sigmoid Colon
Periodicity
Signal Transduction
Homeostasis
Signal transduction
Titration
Amplification
Integrated circuits
Genes
Switches
Feedback
Kinetics
Networks (circuits)

Keywords

  • Hill coefficient
  • Motif
  • Response coefficient
  • Sigmoid
  • Ultrasensitivity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Neuroscience(all)
  • Immunology
  • Medicine(all)

Cite this

Ultrasensitive response motifs : Basic amplifiers in molecular signalling networks. / Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E.

In: Open Biology, Vol. 3, No. APR, 130031, 2013.

Research output: Research - peer-reviewArticle

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