Global Phosphoproteomic Analysis of Insulin/Akt/mTORC1/S6K Signaling in Rat Hepatocytes

• DOI: 10.1021/acs.jproteome.7b00140
• Publication Date: 2017-07-09T15:13:27Z
• Authors: Yuanyuan Zhang; Yajie Zhang; Yonghao Yu
• Keywords: Proto-Oncogene Proteins c-akt

Insulin resistance is a hallmark of type 2 diabetes. Although multiple genetic and physiological factors interact to cause insulin resistance, deregulated signaling by phosphorylation common underlying mechanism. In particular, the specific phosphorylation-dependent regulatory mechanisms outputs are poorly understood in hepatocytes, which represents one most important insulin-responsive cell types. Using primary rat hepatocytes as model system, we performed reductive dimethylation (ReDi)-based quantitative mass spectrometric analysis characterized phosphoproteome that regulated well its key downstream kinases including Akt, mTORC1, S6K. We identified total 12 294 unique, confidently localized sites 3805 phosphorylated proteins this single type. Detailed bioinformatic on each individual data set both known previously unrecognized targets effector pathway. Furthermore, integrated hepatic Akt/mTORC1/S6K axis allowed delineation substrate specificity several close-related within expect sets will serve an invaluable resource, providing foundation for future hypothesis-driven research helps delineate molecular underlie pathogenesis diabetes related metabolic syndrome.