Load-induced modulation of signal transduction networks. Jiang, A., Ventura, A. C., Sontag, E. D., Merajver, S. D., Ninfa, A. J., & Del Vecchio, D. Science Signaling, 4, issue 194:ra67, 2011.
abstract   bibtex   
Biological signal transduction networks are commonly viewed as circuits that pass along in the process amplifying signals, enhancing sensitivity, or performing other signal-processing 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 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
@ARTICLE{ddv11,
   AUTHOR       = {A.C. Jiang and A. C. Ventura and E. D. Sontag and 
      S. D. Merajver and A. J. Ninfa and Del Vecchio, D.},
   JOURNAL      = {Science Signaling},
   TITLE        = {Load-induced modulation of signal transduction networks},
   YEAR         = {2011},
   OPTMONTH     = {},
   OPTNOTE      = {},
   OPTNUMBER    = {},
   PAGES        = {ra67},
   VOLUME       = {4, issue 194},
   KEYWORDS     = {systems biology, biochemical networks, 
      synthetic biology, futile cycles, singular perturbations, modularity},
   PDF          = {../../FTPDIR/delvecchio_etc_science_signaling2011.pdf},
   ABSTRACT     = {Biological signal transduction networks are commonly 
      viewed as circuits that pass along in the process amplifying signals, 
      enhancing sensitivity, or performing other signal-processing 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 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}
}

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