Global phosphoproteomics identifies a major role for AKT and 14-3-3 in regulating EDC3
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.
|ISBN||1535-9484 (Electronic) 1535-9476 (Linking)|
|Authors||Larance, M.; Rowland, A. F.; Hoehn, K. L.; Humphreys, D. T.; Preiss, T.; Guilhaus, M.; James, D. E.;|
|Responsible Garvan Author|
|Publisher Name||MOLECULAR & CELLULAR PROTEOMICS|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20051463|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/10611|