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Push-Pull and Feedback Mechanisms Can Align Signaling System Outputs with Inputs.

Steven S Andrews1, William J Peria2, Richard C Yu3

  • 1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA; The Molecular Sciences Institute, Berkeley, CA 94704, USA.

Cell Systems
|November 30, 2016
PubMed
Summary

Dose-response alignment (DoRA) in cell signaling ensures downstream output matches receptor input. Push-pull mechanisms, not feedback loops, enable perfect DoRA for precise information transfer.

Keywords:
Saccharomyces cervisiaecell signalingdose response alignmentparadoxical signalingpheromone response systempush-pullyeast

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Area of Science:

  • Biochemistry
  • Systems Biology
  • Cell Signaling

Background:

  • Cell signaling systems often display dose-response alignment (DoRA).
  • DoRA aligns downstream signaling output with the fraction of occupied receptors.
  • This alignment enhances the fidelity of transmitted dose information.

Purpose of the Study:

  • To systematically identify biochemical network topologies that generate DoRA.
  • To understand the mechanisms underlying dose-response alignment in biological systems.

Main Methods:

  • Computational analysis of various biochemical network topologies.
  • Systematic search for network structures capable of producing DoRA.
  • Investigation of feedback and feedforward loop effects on DoRA.

Main Results:

  • Most tested networks, including those with feedback and feedforward loops, did not produce DoRA.
  • Networks incorporating "push-pull" mechanisms enabled perfect DoRA.
  • Feedback networks achieved DoRA only when comparing feedback to input and adjusting output.

Conclusions:

  • Push-pull mechanisms are identified as a non-feedback strategy for achieving perfect DoRA.
  • These findings highlight push-pull as a key mechanism for maximizing information transfer in signaling.
  • Suggests genetic methods to differentiate between feedback and push-pull control in biological systems.