Role of inhibitory proteins as modulators of oscillations in NFB signalling

IET Syst Biol. 2009 Mar;3(2):59-76. doi: 10.1049/iet-syb.2008.0105.

Abstract

The authors discuss the role of the Raf kinase inhibitory protein (RKIP) as a modulator of oscillations in NFB signalling. A mathematical model of the NFB signalling pathway was derived and the Lyapunov-Andronov theory was used to analyse dynamical properties of the system. The analytical results were complemented by predictive numerical simulations. Our results suggest that the nature of oscillations, emerging under sustained stimulation of the system, depends on the interplay between the IB kinase (IKK) stimulation and the inhibitory action of RKIP. The authors found a mathematical relation that defines isoclines in IKK and RKIP levels for which the properties of oscillations are conserved and changes in the stimulation can be compensated by modulating RKIP inhibition. On the other hand, the shifting from the current isocline provokes modulation in either the amplitude (for stronger stimulation) or the frequency (for weaker stimulation).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Computer Simulation
  • I-kappa B Kinase / metabolism*
  • Kinetics
  • Models, Biological*
  • NF-kappa B / metabolism*
  • Phosphatidylethanolamine Binding Protein / metabolism
  • Signal Transduction / physiology*
  • Systems Biology / methods*

Substances

  • NF-kappa B
  • Phosphatidylethanolamine Binding Protein
  • I-kappa B Kinase