Fuzzy Logic Analysis of Kinase Pathway Crosstalk in TNF/EGF/Insulin-Induced Signaling

摘要: When modeling cell signaling networks, a balance must be struck between mechanistic detail and ease of interpretation. In this paper we apply fuzzy logic framework to the analysis large, systematic dataset describing dynamics downstream TNF, EGF, insulin receptors in human colon carcinoma cells. Simulations based on recapitulate most features data generate several predictions involving pathway crosstalk regulation. We uncover relationship MK2 ERK pathways that might account for previously identified pro-survival influence MK2. also find unexpected inhibition IKK following EGF treatment, possibly due down-regulation autocrine signaling. More generally, models are flexible, able incorporate qualitative noisy data, powerful enough produce quantitative new biological insights about operation networks.