Substrate-Induced Modulation of Signal Transduction Networks
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" phenom...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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American Association for the Advancement of Science (AAAS)
2014
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| Online Access: | http://hdl.handle.net/1721.1/86356 https://orcid.org/0000-0001-6472-8576 |
| _version_ | 1811077234831654912 |
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| author | Del Vecchio, Domitilla Jiang, Peng Ventura, Alejandra C. Sontag, Eduardo D. Merajver, Sofia D. Ninfa, Alexander J. |
| author2 | Massachusetts Institute of Technology. Department of Mechanical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Mechanical Engineering Del Vecchio, Domitilla Jiang, Peng Ventura, Alejandra C. Sontag, Eduardo D. Merajver, Sofia D. Ninfa, Alexander J. |
| author_sort | Del Vecchio, Domitilla |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:39:47Z |
| format | Article |
| id | mit-1721.1/86356 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:39:47Z |
| publishDate | 2014 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/863562022-09-27T14:04:43Z Substrate-Induced Modulation of Signal Transduction Networks Load-Induced Modulation of Signal Transduction Networks Del Vecchio, Domitilla Jiang, Peng Ventura, Alejandra C. Sontag, Eduardo D. Merajver, Sofia D. Ninfa, Alexander J. Massachusetts Institute of Technology. Department of Mechanical Engineering Del Vecchio, Domitilla Del Vecchio, Domitilla 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. United States. Air Force Office of Scientific Research (Grant FA9550-10-1-0242) 2014-05-02T14:01:19Z 2014-05-02T14:01:19Z 2011-10 2011-05 Article http://purl.org/eprint/type/JournalArticle 1945-0877 1937-9145 http://hdl.handle.net/1721.1/86356 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. https://orcid.org/0000-0001-6472-8576 en_US http://dx.doi.org/10.1126/scisignal.2002152 Science Signaling Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for the Advancement of Science (AAAS) Prof. del Vecchio via Angie Locknar |
| spellingShingle | Del Vecchio, Domitilla Jiang, Peng Ventura, Alejandra C. Sontag, Eduardo D. Merajver, Sofia D. Ninfa, Alexander J. Substrate-Induced Modulation of Signal Transduction Networks |
| title | Substrate-Induced Modulation of Signal Transduction Networks |
| title_full | Substrate-Induced Modulation of Signal Transduction Networks |
| title_fullStr | Substrate-Induced Modulation of Signal Transduction Networks |
| title_full_unstemmed | Substrate-Induced Modulation of Signal Transduction Networks |
| title_short | Substrate-Induced Modulation of Signal Transduction Networks |
| title_sort | substrate induced modulation of signal transduction networks |
| url | http://hdl.handle.net/1721.1/86356 https://orcid.org/0000-0001-6472-8576 |
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