Akt-mediated phosphorylation of argonaute 2 downregulates cleavage and upregulates translational repression of MicroRNA targets

Mol Cell. 2013 May 9;50(3):356-67. doi: 10.1016/j.molcel.2013.03.015. Epub 2013 Apr 18.


A high-throughput RNA interference (RNAi) screen targeting 542 genes of the human kinome was used to discover regulators of RNAi. Here we report that the proto-oncogene Akt-3/PKBγ (Akt3) phosphorylates Argonaute 2 (Ago2) at S387, which downregulates cleavage and upregulates translational repression of endogenous microRNA (miRNA)-targeted messenger RNAs (mRNAs). We further demonstrate that Akt3 coimmunoprecipitates with Ago2 and phosphorylation of Ago2 at S387 facilitates its interaction with GW182 and localization to cytoplasmic processing bodies (P bodies), where miRNA-targeted mRNAs are thought to be stored and degraded. Therefore, Akt3-mediated phosphorylation of Ago2 is a molecular switch between target mRNA cleavage and translational repression activities of Ago2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Argonaute Proteins / genetics*
  • Argonaute Proteins / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Down-Regulation
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • MicroRNAs / genetics*
  • Phosphorylation
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Up-Regulation


  • AGO2 protein, human
  • Argonaute Proteins
  • MAS1 protein, human
  • MicroRNAs
  • Proto-Oncogene Mas
  • AKT3 protein, human
  • Proto-Oncogene Proteins c-akt