Global phosphoproteomics identifies a major role for AKT and 14-3-3 in regulating EDC3

Mark Larance (Lead / Corresponding author), Alexander F. Rowland, Kyle L. Hoehn, David T. Humphreys, Thomas Preiss, Michael Guilhaus, David E. James (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    30 Citations (Scopus)

    Abstract

    Insulin plays an essential role in metabolic homeostasis in mammals, and many of the underlying biochemical pathways are regulated via the canonical phosphatidylinositol 3-kinase/AKT pathway. To identify novel metabolic actions of insulin, we conducted a quantitative proteomics analysis of insulin-regulated 14-3-3-binding proteins in muscle cells. These studies revealed a novel role for insulin in the post-transcriptional regulation of mRNA expression. EDC3, a component of the mRNA decay and translation repression pathway associated with mRNA processing bodies, was shown to be phosphorylated by AKT downstream of insulin signaling. The major insulin-regulated site was mapped to Ser-161, and phosphorylation at this site led to increased 14-3-3 binding. Functional studies indicated that induction of 14-3-3 binding to EDC3 causes morphological changes in processing body structures, inhibition of microRNA-mediated mRNA post-transcriptional regulation, and alterations in the protein- protein interactions of EDC3. These data highlight an important new arm of the insulin signaling cascade in the regulation of mRNA utilization.
    Original languageEnglish
    Pages (from-to)682-694
    Number of pages13
    JournalMolecular & Cellular Proteomics
    Volume9
    Issue number4
    DOIs
    Publication statusPublished - Apr 2010

    Keywords

    • Animals
    • 14-3-3 Proteins
    • MicroRNAs
    • Cricetulus
    • Humans
    • Ribonucleoproteins, Small Nuclear
    • RNA Stability
    • Mice
    • NIH 3T3 Cells
    • Binding Sites
    • Oncogene Protein v-akt
    • Protein Interaction Mapping
    • Phosphorylation
    • Phosphoproteins
    • Cells, Cultured
    • Proteomics
    • CHO Cells
    • Gene Expression Regulation
    • RNA Interference
    • Cricetinae

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  • Cite this

    Larance, M., Rowland, A. F., Hoehn, K. L., Humphreys, D. T., Preiss, T., Guilhaus, M., & James, D. E. (2010). Global phosphoproteomics identifies a major role for AKT and 14-3-3 in regulating EDC3. Molecular & Cellular Proteomics, 9(4), 682-694. https://doi.org/10.1074/mcp.M900435-MCP200