Ultrasensitivity in signaling cascades revisited: Linking local and global ultrasensitivity estimations

Edgar Altszyler, Alejandra C Ventura, Alejandro Colman-Lerner and Ariel Chernomoretz

PLOS ONE, 2017, vol. 12, issue 6, 1-18

Abstract: Ultrasensitive response motifs, capable of converting graded stimuli into binary responses, are well-conserved in signal transduction networks. Although it has been shown that a cascade arrangement of multiple ultrasensitive modules can enhance the system’s ultrasensitivity, how a given combination of layers affects a cascade’s ultrasensitivity remains an open question for the general case. Here, we introduce a methodology that allows us to determine the presence of sequestration effects and to quantify the relative contribution of each module to the overall cascade’s ultrasensitivity. The proposed analysis framework provides a natural link between global and local ultrasensitivity descriptors and it is particularly well-suited to characterize and understand mathematical models used to study real biological systems. As a case study, we have considered three mathematical models introduced by O’Shaughnessy et al. to study a tunable synthetic MAPK cascade, and we show how our methodology can help modelers better understand alternative models.

Date: 2017
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Citations: View citations in EconPapers (1)

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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0180083

DOI: 10.1371/journal.pone.0180083

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