Long Signaling Cascades Tend to Attenuate Retroactivity
Name
del Vecchio_Long signaling.pdf
Size
334.14 KB
Format
Adobe PDF
Checksum (MD5)
aff17e06eac0f436d9f485838dd56f51
Author(s)
Ossareh, Hamid R.
Ventura, Alejandra C.
Merajver, Sofia D.
Del Vecchio, Domitilla
Date Issued
April 2011
Journal
Biophysical Journal
Publisher
Elsevier
Citation
Ossareh, Hamid R., Alejandra C. Ventura, Sofia D. Merajver, and Domitilla Del Vecchio. “Long Signaling Cascades Tend to Attenuate Retroactivity.” Biophysical Journal 100, no. 7 (April 2011): 1617–1626. © 2011 Biophysical Society
Version
Final published version
Abstract
Signaling pathways consisting of phosphorylation/dephosphorylation cycles with no explicit feedback allow signals to propagate not only from upstream to downstream but also from downstream to upstream due to retroactivity at the interconnection between phosphorylation/dephosphorylation cycles. However, the extent to which a downstream perturbation can propagate upstream in a signaling cascade and the parameters that affect this propagation are presently unknown. Here, we determine the downstream-to-upstream steady-state gain at each stage of the signaling cascade as a function of the cascade parameters. This gain can be made smaller than 1 (attenuation) by sufficiently fast kinase rates compared to the phosphatase rates and/or by sufficiently large Michaelis-Menten constants and sufficiently low amounts of total stage protein. Numerical studies performed on sets of biologically relevant parameters indicated that ~50% of these parameters could give rise to amplification of the downstream perturbation at some stage in a three-stage cascade. In an n-stage cascade, the percentage of parameters that lead to an overall attenuation from the last stage to the first stage monotonically increases with the cascade length n and reaches 100% for cascades of length at least 6.
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.bpj.2011.02.014
