TY - JOUR
T1 - Global phosphoproteomics identifies a major role for AKT and 14-3-3 in regulating EDC3
AU - Larance, Mark
AU - Rowland, Alexander F.
AU - Hoehn, Kyle L.
AU - Humphreys, David T.
AU - Preiss, Thomas
AU - Guilhaus, Michael
AU - James, David E.
PY - 2010/4
Y1 - 2010/4
N2 - 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 insulinregulated 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 proteinprotein interactions of EDC3. These data highlight an important new arm of the insulin signaling cascade in the regulation of mRNA utilization.
AB - 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 insulinregulated 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 proteinprotein interactions of EDC3. These data highlight an important new arm of the insulin signaling cascade in the regulation of mRNA utilization.
UR - http://www.scopus.com/inward/record.url?scp=77950664407&partnerID=8YFLogxK
U2 - 10.1074/mcp.M900435-MCP200
DO - 10.1074/mcp.M900435-MCP200
M3 - Article
SN - 1535-9476
VL - 9
SP - 682
EP - 694
JO - Molecular and Cellular Proteomics
JF - Molecular and Cellular Proteomics
IS - 4
ER -