Substrate-Induced Modulation of Signal Transduction Networks
Author(s)
Del Vecchio, Domitilla; Jiang, Peng; Ventura, Alejandra C.; Sontag, Eduardo D.; Merajver, Sofia D.; Ninfa, Alexander J.; ... Show more Show less
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Alternative title
Load-Induced Modulation of Signal Transduction Networks
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Biological signal transduction networks are commonly viewed as circuits that pass along information—in the process amplifying signals, enhancing sensitivity, or performing other signal-processing tasks—to transcriptional and other components. Here, we report on a "reverse-causality" phenomenon, which we call load-induced modulation. Through a combination of analytical and experimental tools, we discovered that signaling was modulated, in a surprising way, by downstream targets that receive the signal and, in doing so, apply what in physics is called a load. Specifically, we found that non-intuitive changes in response dynamics occurred for a covalent modification cycle when load was present. Loading altered the response time of a system, depending on whether the activity of one of the enzymes was maximal and the other was operating at its minimal rate or whether both enzymes were operating at submaximal rates. These two conditions, which we call "limit regime" and "intermediate regime," were associated with increased or decreased response times, respectively. The bandwidth, the range of frequency in which the system can process information, decreased in the presence of load, suggesting that downstream targets participate in establishing a balance between noise-filtering capabilities and a circuit’s ability to process high-frequency stimulation. Nodes in a signaling network are not independent relay devices, but rather are modulated by their downstream targets.
Date issued
2011-10Department
Massachusetts Institute of Technology. Department of Mechanical EngineeringJournal
Science Signaling
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Jiang, P., A. C. Ventura, E. D. Sontag, S. D. Merajver, A. J. Ninfa, and D. Del Vecchio. “Load-Induced Modulation of Signal Transduction Networks.” Science Signaling 4, no. 194 (October 11, 2011): ra67–ra67.
Version: Author's final manuscript
ISSN
1945-0877
1937-9145