Robustness of the signal transduction system of the mammalian JAK/STAT pathway and dimerization steps

Emi Shudo, Jin Yang, Akihiko Yoshimura, Yoh Iwasa

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


In the interferon-γ (IFNγ)-activated Janus Kinase (JAK)/signal transducer and activator of transcription 1 (STAT1) pathway, multiple steps of STAT1 dimerization are required prior to gene expression that produce antiviral molecules. By interpreting experimental results, an existing mathematical model suggested that only phosphorylated STAT1 dimers could translocate to the nucleus and activate gene transcription. In this paper, we examine the role of STAT1 dimerization steps by studying the dynamic behaviors of four alternative models. By analyzing several system properties at low input IFNγ signal including the steady-state antiviral molecule production, to the input, the delay of responses triggered by input, and the parameter sensitivity, we found that the mice JAK/STAT1 system identified by experiments (1) suppresses antiviral molecule production at low input signal, (2) has slow kinetics of antiviral molecule production and (3) has low parameter sensitivity of antiviral molecule production at steady state. We conclude that the observed structure of the JAK/STAT1 pathway is responsible for the robust system behavior.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalJournal of Theoretical Biology
Issue number1
Publication statusPublished - 2007 May 7
Externally publishedYes


  • Dimerization
  • JAK/STAT pathway
  • Negative feedback
  • Robust system

ASJC Scopus subject areas

  • Statistics and Probability
  • Modelling and Simulation
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Agricultural and Biological Sciences
  • Applied Mathematics


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