System theoretical investigation of human epidermal growth factor receptor-mediated signalling

IET Syst Biol. 2008 Sep;2(5):273-84. doi: 10.1049/iet-syb:20080116.

Abstract

The partitioning of biological networks into coupled-functional modules is being increasingly applied for developing predictive models of biological systems. This approach has the advantage that predicting a system-level response does not require a mechanistic description of the internal dynamics of each module. Identification of the input-output characteristics of the network modules and the connectivity between the modules provide the necessary quantitative representation of system dynamics. However, the determination of the input-output relationships of the modules is not trivial; it requires the controlled perturbation of module inputs and systematic analysis of experimental data. In this report, the authors apply a system theoretical analysis approach to derive the time-dependent input-output relationships of the functional module for the human epidermal growth factor receptor (HER) mediated Erk and Akt signalling pathways. Using a library of cell lines expressing endogenous levels of epidermal growth factor receptor (EGFR) and varying levels of HER2, the authors show that a transfer function-based representation can be successfully applied to quantitatively characterise information transfer in this system.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Line
  • Computer Simulation
  • Epithelial Cells / metabolism*
  • ErbB Receptors / metabolism*
  • Humans
  • Models, Biological*
  • Receptor, ErbB-2 / metabolism*
  • Signal Transduction / physiology*
  • Systems Biology / methods

Substances

  • EGFR protein, human
  • ErbB Receptors
  • Receptor, ErbB-2