System theoretical investigation of human epidermal growth factor receptor-mediated signalling.
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.
Zhang
Y
Y
Pacific Northwest National Laboratory, Computational Biology and Bioinformatics Group, Richland, WA 99352, USA.
Shankaran
H
H
Opresko
L
L
Resat
H
H
D002460:Cell Line; D003198:Computer Simulation; D004847:Epithelial Cells / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D049490:Systems Biology / Q000379:methods
D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human