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.
Bibliographical noteFunding 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.
- Probability in signaling
- Receptor tyrosine kinase
- SH2 domain
- SH3 domain
ASJC Scopus subject areas
- Molecular Biology