Fig. 8

Construction of an ANIMO model of signal transduction events in human colon carcinoma cells upon stimulation with 100 ng/ml TNF α. Graphs below show the dynamic behaviour of the corresponding models above, comparing it to the measured activity values from [26] (error bars represent the standard deviation). On the vertical axis, “100” represents the maximum protein activity in the complete experiment. A red vertical line in each graph highlights an arbitrary time point in the time course: nodes in the corresponding model are coloured according to their activity at that time point. a, d Basic model showing direct activation of JNK1 and MK2 by TNF α. No peak dynamics are observed because no inactivating processes are present. b, e The model after addition of inactivating phosphatases and a negative feedback loop that down-regulates TNFR. Note that adding TNFR internalization or phosphatases alone would not be enough to reproduce activity peaks. c, f The model after addition of IKK, IL1-secretion (abstracting the autocrine IL-1 signalling described in [27]), Casp8 and Casp3, showing the late response to TNF α signalling. As the data set did not contain values for cleaved caspase-3, but only for its non-cleaved precursor pro-caspase-3, we computed the Casp3_data series as 100 %−[pro-Casp3]