title: Model-based analysis of interferon-beta induced signaling pathway.
abstract: BACKGROUND
  Interferon-beta induced JAK-STAT signaling pathways contribute to mucosal immune recognition and an anti-viral state. Though the main molecular mechanisms constituting these pathways are known, neither the detailed structure of the regulatory network, nor its dynamics has yet been investigated. The objective of this work is to build a mathematical model for the pathway that would serve two purposes: (1) to reproduce experimental results in simulation of both early and late response to Interferon-beta stimulation and (2) to explain experimental phenomena generating new hypotheses about regulatory mechanisms that cannot yet be tested experimentally.
  
  
  RESULTS
  Experimentally determined time dependent changes in the major components of this pathway were used to build a mathematical model describing pathway dynamics in the form of ordinary differential equations. The experimental results suggested existence of unknown negative control mechanisms that were tested numerically using the model. Together, experimental and numerical data show that the epithelial JAK-STAT pathway might be subjected to previously unknown dynamic negative control mechanisms: (1) activation of dormant phosphatases and (2) inhibition of nuclear import of IRF1.
authors: Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland. jaroslaw.smieja@polsl.pl
authors: Jaroslaw
authors: J
authors: Smieja
authors: Mohammad
authors: M
authors: Jamaluddin
authors: Allan R
authors: AR
authors: Brasier
authors: Marek
authors: M
authors: Kimmel
mesh_terms: D006367:HeLa Cells; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism*; D053612:Janus Kinases / Q000378:metabolism; D008954:Models, Biological; D015398:Signal Transduction
chemical_list: D016899:Interferon-beta; D053612:Janus Kinases