Fig. 6

Signalling network downstream of TNF α and EGF in human colon carcinoma cells: improved model. a The model for the merged TNF α and EGF pathways after addition of the two hypotheses (highlighted). Hypothesis 1 assumes IL-1 α expression to depend on AP-1 activity, which in turn requires both c-Jun en c-Fos to be activated by JNK1 and ERK, respectively. Hypothesis 2 assumes RAS as an activator of MEKK1. Node colours represent the activity levels 15 minutes after stimulation of 100 ng/ml TNF α + 100 ng/ml EGF. b After the addition of the first hypothesis (activation of IL-1 α production depending both on JNK1 and ERK): production of IL-1 α after stimulation with 100 ng/ml TNF α (series IL-1a (TNFa)) compared with stimulation with 100 ng/ml TGF α (series IL-1a (TGFa)) (24 h). The IL-1a (TGFa) series is always 0. c After the addition of the second hypothesis (activation of MEKK1 downstream of EGFR): activation of JNK1 and MK2 after stimulation with 5 ng/ml TNF α + 10 μg/ml C225 (2 hours). The JNK1 series is always 0. Additional file 1: Section B.3 explains how the dosage of 5 ng/ml TNF α was represented in the model. The _data suffix identifies experimental data; all other series are computed by ANIMO