Physical EGFR interactome generation and core network proteins identification. Physical EGFR interactome generation and core network proteins identification. (A) The interactome (N=263 proteins) was derived from TAP‐LC‐MS/MS experiments with bait proteins (blue rectangles). Yellow ellipse nodes indicate prey proteins directly identified from TAP experiments, while nodes with red border are from both pY and TAP experiments. Tyrosine phosphorylated proteins significantly perturbed by erlotinib identified from pY experiments, and are shown as green ellipses, including EGFR, SHC1, and ERBB3. Green ellipses indicate proteins identified from pY experiments that were added to the network based on the public interactions database. Phosphotyrosine sites significantly perturbed by erlotinib (n=62) are indicated as blue circles connected to the relevant protein. Gray lines between proteins indicate bait–prey relationships derived by TAP experiments or literature‐reported interactions between bait or prey proteins identified by TAP and pY containing proteins identified by phosphoproteomics. (B) Functional categories and number of proteins for each particular association. (C, top) Effects of RNAi analyses on cell viability across PC9, HCC827, and HCC4006 lung cancer cells and overlapping proteins represented in Venn diagram. (C, bottom) Characteristics of 14 significant proteins found in common among all 3 EGFR‐mutant cell lines. (D) Core network proteins were mapped back onto the EGFR interactome. Right panels show effects of core network protein knockdown on ERK and AKT phosphorylation assayed through in‐cell western analysis. Source data for this figure is available on the online supplementary information page. Jiannong Li et al. Mol Syst Biol 2013;9:705 © as stated in the article, figure or figure legend