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

Emi Shudo, Jin Yang, Akihiko Yoshimura, Yoh Iwasa

研究成果: Article査読

9 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1-9
ページ数9
ジャーナルJournal of Theoretical Biology
246
1
DOI
出版ステータスPublished - 2007 5月 7
外部発表はい

ASJC Scopus subject areas

  • 統計学および確率
  • モデリングとシミュレーション
  • 生化学、遺伝学、分子生物学一般
  • 免疫学および微生物学一般
  • 農業および生物科学一般
  • 応用数学

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