The regulatory circuits for hysteretic switching in cellular signal transduction pathways

Jeong Rae Kim, Kwang Hyun Cho

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Hysteresis can be found in many physical systems, and a hysteretic switch has been used for various mechanical and electrical systems. Such a hysteretic switch can be created by using a single positive feedback loop, as often used in engineering systems. It is, however, intriguing that various cellular signaling systems use coupled positive feedback loops to implement the hysteretic switch. A question then arises about the advantage of using coupled positive feedback loops instead of simple isolated positive feedback for an apparently equivalent hysteretic switch. Through mathematical simulations, we determined that cellular systems with coupled positive feedback loops show enhanced hysteretic switching, and can thereby make a more reliable decision under conditions of noisy signaling. As most intracellular processes are accompanied by intrinsic noise, important cellular decisions such as differentiation and apoptosis need to be highly robust to such noises. The coupled positive feedback loops might have been evolutionarily acquired to enable correct cell fate decisions to be made through enhanced hysteretic switching in noisy cellular environments.

Original languageEnglish
Pages (from-to)3329-3337
Number of pages9
JournalFEBS Journal
Issue number18
StatePublished - Sep 2012


  • hysteresis
  • positive feedback
  • robustness
  • signal transduction pathway
  • switching system


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