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Dynamic adipocyte phosphoproteome reveals that Akt directly regulates mTORC2

Abstract

A major challenge of the post-genomics era is to define the connectivity of protein phosphorylation networks. Here, we quantitatively delineate the insulin signaling network in adipocytes by high-resolution mass spectrometry-based proteomics. These data reveal the complexity of intracellular protein phosphorylation. We identified 37,248 phosphorylation sites on 5,705 proteins in this single-cell type, with approximately 15% responding to insulin. We integrated these large-scale phosphoproteomics data using a machine learning approach to predict physiological substrates of several diverse insulin-regulated kinases. This led to the identification of an Akt substrate, SIN1, a core component of the mTORC2 complex. The phosphorylation of SIN1 by Akt was found to regulate mTORC2 activity in response to growth factors, revealing topological insights into the Akt/mTOR signaling network. The dynamic phosphoproteome described here contains numerous phosphorylation sites on proteins involved in diverse molecular functions and should serve as a useful functional resource for cell biologists.

Type Journal
Authors Humphrey, S. J.; Yang, G.; Yang, P.; Fazakerley, D. J.; Stockli, J.; Yang, J. Y.; James, D. E.
Publisher Name CELL METAB
Published Date 2013-06-16 00:00:00
Published Volume 17
Published Issue 6
Published Pages 1009-20
URL http://www.ncbi.nlm.nih.gov/pubmed/23684622
Status Published