A Regulated Double-Negative Feedback Decodes the Temporal Gradient of Input Stimulation in a Cell Signaling Network

Sang-Min Park; Sung-Young Shin; Kwang-Hyun Cho

doi:10.1371/journal.pone.0162153

A Regulated Double-Negative Feedback Decodes the Temporal Gradient of Input Stimulation in a Cell Signaling Network

PLoS One. 2016 Sep 1;11(9):e0162153. doi: 10.1371/journal.pone.0162153. eCollection 2016.

Authors

Sang-Min Park¹, Sung-Young Shin^{1

2

3}, Kwang-Hyun Cho¹

Affiliations

¹ Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.
² Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, 3800, Australia.
³ Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.

Abstract

Revealing the hidden mechanism of how cells sense and react to environmental signals has been a central question in cell biology. We focused on the rate of increase of stimulation, or temporal gradient, known to cause different responses of cells. We have investigated all possible three-node enzymatic networks and identified a network motif that robustly generates a transient or sustained response by acute or gradual stimulation, respectively. We also found that a regulated double-negative feedback within the motif is essential for the temporal gradient-sensitive switching. Our analysis highlights the essential structure and mechanism enabling cells to properly respond to dynamic environmental changes.

MeSH terms

Feedback, Physiological*
Signal Transduction*

Grants and funding

This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea Government, the Ministry of Science, ICT & Future Planning (2015M3A9A7067220, 2014R1A2A1A10052404 and 2013M3A9A7046303). This work was also supported by the KUSTAR-KAIST Institute, Korea, under the R&D program supervised by the KAIST, the grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI13C2162), and the KAIST Future Systems Healthcare Project from the Ministry of Science, ICT and Future Planning. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.