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Cell Metab. 2013 Jun 4;17(6):1009-20. doi: 10.1016/j.cmet.2013.04.010. Epub 2013 May 16.

Dynamic adipocyte phosphoproteome reveals that Akt directly regulates mTORC2.

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1
Diabetes and Obesity Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.

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.

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PMID:
23684622
PMCID:
PMC3690479
DOI:
10.1016/j.cmet.2013.04.010
[Indexed for MEDLINE]
Free PMC Article

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