Global and Targeted Quantification of Seven Human Cell Lines Reveals the Correlation of Cell Type- Specific Responses with Feedback Regulators

摘要

Global proteomics quantified ～3,000 proteins across 7 cell lines. However, it still lacks sensitivity for low-abundance pathway proteins in that only 11 out of 32 EGFR proteins were reliably detected. Ultrasensitive PRISM-SRM allows accurate measurements of all 32 EGFR pathway proteins across 7 cell lines. The advantages of targeted quantification in terms of sensitivity, accuracy, and dynamic range were clearly demonstrated. Among the 32 proteins, the stoichiometric differences can be >1,000-fold (e.g., EGFR vs. DUSP6). Differential ERK responses were observed to correlate most strongly with the abundances of several feedback regulators, which suggests that cell-specific expression of feedback regulators of the EGFR pathway is most likely responsible for the cell type-specific differences observed in ERK activation.