Deactivation of src family kinases: Hypothesis testing using a Monte Carlo sensitivity analysis of systems-level properties

Hendrik Fuss, Werner Dubitzky, Stephen Downes, Mary Jo Kurth

    Research output: Contribution to journalArticle

    7 Citations (Scopus)

    Abstract

    Src family tyrosine kinases play a key role in many cellular signalling networks, but due to the high complexity of these networks their precise function remains elusive. Many factors involved in Src regulation, such as specific kinases and phosphatases, are still unknown. Mathematical models have been constructed to improve the understanding of the system and its dynamic behavior. Using a computational random parameter search, we characterized and compared the dynamics of three alternative models in order to assess their likelihoods. For this, we investigated how systems-level properties such as bistability and excitable behavior relate to kinetic and physiological parameters and how robust these properties were. Our results suggest the existence of a putative negative feedback loop in the Src system. A previously suggested role for PTP. in the deactivation of Src was not supported by the model.
    LanguageEnglish
    Pages1185-1200
    JournalJournal of Computational Biology
    Volume14
    Issue number9
    DOIs
    Publication statusPublished - Nov 2007

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    systems analysis
    phosphotransferases (kinases)
    cell communication
    tyrosine
    mathematical models
    testing
    kinetics

    Cite this

    Fuss, Hendrik ; Dubitzky, Werner ; Downes, Stephen ; Kurth, Mary Jo. / Deactivation of src family kinases: Hypothesis testing using a Monte Carlo sensitivity analysis of systems-level properties. In: Journal of Computational Biology. 2007 ; Vol. 14, No. 9. pp. 1185-1200.
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    abstract = "Src family tyrosine kinases play a key role in many cellular signalling networks, but due to the high complexity of these networks their precise function remains elusive. Many factors involved in Src regulation, such as specific kinases and phosphatases, are still unknown. Mathematical models have been constructed to improve the understanding of the system and its dynamic behavior. Using a computational random parameter search, we characterized and compared the dynamics of three alternative models in order to assess their likelihoods. For this, we investigated how systems-level properties such as bistability and excitable behavior relate to kinetic and physiological parameters and how robust these properties were. Our results suggest the existence of a putative negative feedback loop in the Src system. A previously suggested role for PTP. in the deactivation of Src was not supported by the model.",
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    Deactivation of src family kinases: Hypothesis testing using a Monte Carlo sensitivity analysis of systems-level properties. / Fuss, Hendrik; Dubitzky, Werner; Downes, Stephen; Kurth, Mary Jo.

    In: Journal of Computational Biology, Vol. 14, No. 9, 11.2007, p. 1185-1200.

    Research output: Contribution to journalArticle

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