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 journalArticle

8 Citations (Scopus)

Abstract

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
Volume246
Issue number1
DOIs
Publication statusPublished - 2007 May 7
Externally publishedYes

Fingerprint

non-specific protein-tyrosine kinase
STAT1 Transcription Factor
Janus Kinases
Signal transduction
dimerization
Dimerization
Signal Transduction
Transcription
signal transduction
Pathway
transcription (genetics)
Antiviral Agents
Transducer
Transducers
Robustness
Molecules
Interferons
Parameter Sensitivity
interferons
Gene expression

Keywords

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

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Robustness of the signal transduction system of the mammalian JAK/STAT pathway and dimerization steps. / Shudo, Emi; Yang, Jin; Yoshimura, Akihiko; Iwasa, Yoh.

In: Journal of Theoretical Biology, Vol. 246, No. 1, 07.05.2007, p. 1-9.

Research output: Contribution to journalArticle

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