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Robustness Analysis of the IFN-γ Induced JAK-STAT Signaling Pathway

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Abstract

Here, the issue of robustness analysis of cell JAK-STAT signal transduction networks is addressed. This is investigated upon a mathematical model of IFN-γ induced JAK-STAT signaling pathway by applying robustness analysis which is based on a broad range of simultaneous and systematical parameters variation. The effects of the variations of the initial signal proteins' concentrations on the output of this system are also studied. The study demonstrates that the JAK-STAT signaling pathway is robust with respect to its “signal time” and “signal duration”, but sensitive with respect to its “signal amplitude”. These analysis results can point to experimental designs that can further test how the pathway activity can be perturbed.

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References

  1. Bhalla U S, Iyengar R. Emergent properties of networks of biological signaling pathways. Science, 1999, 283: 381–387.

    Google Scholar 

  2. Bhalla U S, Iyengar R. Robustness of the bistable behavior of a biological signaling feedback loop. Chaos, 2001, 11: 221–226.

    Article  Google Scholar 

  3. Cho K H, Shin S Y, Lee H W et al. Investigations into the analysis and modeling of the TNF alpha-mediated NF-kappa B-signaling pathway. Genome Res., 2003, 13: 2413–2422.

    Article  Google Scholar 

  4. Kholodenko B N, Demin O V, Moehren G, Hoek J B. Quantification of short term signaling by the epidermal growth factor receptor. J. Biol. Chem., 1999, 274: 30169–30181.

    Article  Google Scholar 

  5. Swameye I, Muller T G, Timmer J, Sandra O, Klingmuller U. Identification of nucleocytoplasmic cycling as a remote sensor in cellular signaling by databased modeling. In Proc. Natl. Acad. Sci., U.S.A., 2003, 100: 1028–1033.

  6. Darnell J E Jr. STATs and gene regulation. Science, 1997, 277: 1630–1635.

    Google Scholar 

  7. Levy D E, Darnell J E Jr. Stats: Transcriptional control and biological impact. Nat. Rev. Mol. Cell Biol., 2002, 3: 651–662.

    Article  Google Scholar 

  8. Shuai K, Liu B. Regulation of JAK-STAT signalling in the immune system. Nat. Rev. Immunol., 2003, 3: 900–911.

    Article  Google Scholar 

  9. Shuai K. The STAT family of proteins in cytokine signaling. Prog. Biophys. Mol. Biol., 1999, 71: 405–422.

    Google Scholar 

  10. O'Shea J J, Gadina M, Schreiber R D. Cytokine signaling in 2002: New surprises in the Jak/Stat pathway. Cell, 2002, 109(Suppl): S121–S131.

    Google Scholar 

  11. Boehm U, Klamp T, Groot M, Howard J C. Cellular responses to interferon-gamma. Annu. Rev. Immunol., 1997, 15: 749–795.

    Article  Google Scholar 

  12. Yamada S, Shiono S, Joo A, Yoshimura A. Control mechanism of JAK/STAT signal transduction pathway. FEBS Lett., 2003, 534: 190–196.

    Article  Google Scholar 

  13. Chatterjee-Kishore M, Wright K L, Ting J P, Stark G R. How Stat1 mediates constitutive gene expression: A complex of unphosphorylated Stat1 and IRF1 supports transcription of the LMP2 gene. EMBO J., 2000, 19: 4111–4122.

    Article  Google Scholar 

  14. Mahboubi K, Pober J S. Activation of signal transducer and activator of transcription 1 (STAT1) is not sufficient for the induction of STAT1-dependent genes in endothelial cells. Comparison of interferon-gamma and oncostatin M. J. Biol. Chem., 2002, 277: 8012–8021.

    Article  Google Scholar 

  15. Heinrich R, Neel B G, Rapoport T A. Mathematical models of protein kinase signal transduction. Mol. Cell, 2002, 9: 957–970.

    Article  Google Scholar 

  16. Barkai N, Leibler S. Robustness in simple biochemical networks. Nature, 1997, 387: 913–917.

    Google Scholar 

  17. Nils Blüthgen and Hanspeter Herzel. How robust are switches in intracellular signaling cascades? Journal of Theoretical Biology, 2003, 225: 293–300.

    Google Scholar 

  18. Alon U, Surette M G, Barkai N, Leibler S. Robustness in bacterial chemotaxis. Nature, 1999, 397: 168–171.

    Google Scholar 

  19. Andrews R P, Ericksen M B, Cunningham C M, Daines M O, Hershey G K. Analysis of the life cycle of Stat6. Continuous cycling of STAT6 is required for IL-4 signaling. J. Biol. Chem., 2002, 277: 36563–36569.

    Google Scholar 

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Authors and Affiliations

  1. Institute of Bioinformatics and Systems Biology, MOE Key Laboratory of Bioinformatics Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, 100084, P.R. China

    Zhi-Ke Zi & Zhi-Rong Sun

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  1. Zhi-Ke Zi
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  2. Zhi-Rong Sun
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Correspondence to Zhi-Rong Sun.

Additional information

Supported by the National Basic Research 973 Program of China under Grant No.973-2003CB715903 and the National Natural Science Foundation of China under Grant No.NSFC-90303017.

Zhi-Ke Zi is currently a greduate student in the institute of Bioinformatics and Systems Biology, Tsinghua University. His research interests focus on mathematical modeling and dynemic analysis of celluar signaling pathways.

Zhi-Rong Sun obtained his B.S. degree from Tsinghua University in 1970. He became a lacturer in the Automation Department of Tsinghua University after Graduation. He has been working in the Department of Biological Sciences & Technology, Tsinghua University since 1984. He became an associate professor in bioinformation in 1990. He has been a full professor since 1998. He was a visiting sceintist at Birkbeck College in 1992-1993, and a visiting scientist in UIUC in 1997-1998. In the early years of Zhi-Rong Sun's research, he was engaged in the study of control and informatics. After the 1980s he shifted to the area of theoretical molecular biology. In the 1990s, he extended his research to bioinformatics.

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Zi, ZK., Sun, ZR. Robustness Analysis of the IFN-γ Induced JAK-STAT Signaling Pathway. J Comput Sci Technol 20, 491–495 (2005). https://doi.org/10.1007/s11390-005-0491-5

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  • DOI: https://doi.org/10.1007/s11390-005-0491-5

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