Noise in cellular signaling pathways: Causes and effects

John E. Ladbury*, Stefan T. Arold

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

84 Scopus citations

Abstract

Noise caused by stochastic fluctuations in genetic circuits (transcription and translation) is now appreciated as a central aspect of cell function and phenotypic behavior. Noise has also been detected in signaling networks, but the origin of this noise and how it shapes cellular outcomes remain poorly understood. Here, we argue that noise in signaling networks results from the intrinsic promiscuity of protein-protein interactions (PPIs), and that this noise has shaped cellular signal transduction. Features promoted by the presence of this molecular signaling noise include multimerization and clustering of signaling components, pleiotropic effects of gross changes in protein concentration, and a probabilistic rather than a linear view of signal propagation.

Original languageEnglish (US)
Pages (from-to)173-178
Number of pages6
JournalTrends in Biochemical Sciences
Volume37
Issue number5
DOIs
StatePublished - May 2012
Externally publishedYes

Bibliographical note

Funding Information:
We thank Gabor Balazsi, Hiro Akari, the editor and reviewers for their comments and interesting suggestions, and K. Muller for editorial assistance. This research was supported in part by the National Institutes of Health through an MD Anderson Cancer Center Support Grant (CA016672), and by the G. Harold and Leila Y. Mathers Charitable Foundation.

Keywords

  • Evolution
  • Interactome
  • Probability in signaling
  • Receptor tyrosine kinase
  • SH2 domain
  • SH3 domain
  • Specificity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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