Brightman, Fell, 2000

Model Status

This is the initial translation of the model into CellML. Concentrations have no dimensions in order to balance units. The percentage activation variables used to produce the graphs in the paper have not yet been added to this model. The model can therefore run in Opencell and COR but does not reproduce the figures in the paper.

Model Structure

ABSTRACT: Although epidermal growth factor (EGF) induces transient activation of Ras and the mitogen-activated protein kinase (MAPK) cascade in PC12 cells, whereas nerve growth factor (NGF) stimulates sustained activation, the basis for these contrasting responses is not known. We have developed a computer simulation of EGF-induced MAPK cascade activation, which provides quantitative evidence that feedback inhibition of the MAPK cascade is the most important factor in determining the duration of cascade activation. Hence, we propose that the observed quantitative differences in EGF and NGF signalling can be accounted for by differential feedback regulation of the MAPK cascade.

The complete original paper reference is cited below:

Differential feedback regulation of the MAPK cascade underlies the quantitative differences in EGF and NGF signalling in PC12 cells, Frances A. Brightman, David A. Fell, 2000,Federation of European Biochemical Societies Letters, 482(3), 169-174. PubMed ID: 11024454

Schematic representation of the computer simulation of EGF signal transduction.