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Oligopeptide Competition Assay for Phosphorylation Site Determination
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Biphasic responses in multi-site phosphorylation systems.

Thapanar Suwanmajo1, J Krishnan

  • 1Department of Chemical Engineering, Centre for Process Systems Engineering, Imperial College London, , South Kensington Campus, London SW7 2AZ, UK.

Journal of the Royal Society, Interface
|October 11, 2013
PubMed
Summary
This summary is machine-generated.

Distributive multi-site phosphorylation mechanisms can generate biphasic dose-responses due to competing effects. This study clarifies conditions for biphasic responses and mechanism discrimination in cellular signaling.

Keywords:
enzyme sequestrationmulti-site modificationnon-monotonic responseshared enzymesignal processingsubstrate sequestration

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Area of Science:

  • Cellular Biology
  • Biochemistry
  • Systems Biology

Background:

  • Multi-site phosphorylation is crucial for cellular signaling and post-translational modification.
  • Understanding dose-response characteristics is key to deciphering complex cellular processes.

Purpose of the Study:

  • To investigate how distributive multi-site modification by a single kinase/phosphatase pair yields biphasic dose-responses.
  • To identify the underlying competing effects and conditions that promote these responses.
  • To differentiate between various multi-site phosphorylation mechanisms based on their response profiles.

Main Methods:

  • Computational simulations of multi-site phosphorylation models.
  • Mathematical analysis of reaction kinetics.
  • Comparative analysis of different phosphorylation mechanism variants.

Main Results:

  • Distributive mechanisms can exhibit biphasic or partial biphasic dose-response curves for the maximally phosphorylated substrate at steady state.
  • A hidden competing effect was identified as the cause of biphasic behavior.
  • Some multi-site phosphorylation mechanisms inherently cannot produce biphasic responses.
  • Biphasic responses can be combined with threshold and bistable behaviors.

Conclusions:

  • Provides a unified understanding of biphasic response generation in multi-site phosphorylation.
  • Offers criteria for distinguishing between different multi-site phosphorylation mechanisms.
  • Highlights the capacity of multi-site phosphorylation systems for complex signal processing.