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

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)


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.

Original languageEnglish
Article number0162153
Number of pages17
JournalPLoS ONE
Issue number9
Publication statusPublished - 1 Sept 2016


  • network motiffs
  • signaling networks
  • signal processing
  • feedback regulation
  • enzyme regulation
  • enzymes
  • hormone receptor signaling
  • ERK signaling cascade

Cite this