Phosphorylation of Argonaute 2 at serine-387 facilitates its localization to processing bodies.

Ago (Argonaute) proteins are essential effectors of RNA-mediated gene silencing. To explore potential regulatory mechanisms for Ago proteins, we examined the phosphorylation of human Ago2. We identified serine-387 as the major Ago2 phosphorylation site in vivo. Phosphorylation of Ago2 at serine-387 was significantly induced by treatment with sodium arsenite or ...
anisomycin, and arsenite-induced phosphorylation was inhibited by a p38 MAPK (mitogen-activated protein kinase) inhibitor, but not by inhibitors of JNK (c-Jun N-terminal kinase) or MEK [MAPK/ERK (extracellular-signal-regulated kinase) kinase]. MAPKAPK2 (MAPK-activated protein kinase-2) phosphorylated bacterially expressed full-length human Ago2 at serine-387 in vitro, but not the S387A mutant. Finally, mutation of serine-387 to an alanine residue or treatment of cells with a p38 MAPK inhibitor reduced the localization of Ago2 to processing bodies. These results suggest a potential regulatory mechanism for RNA silencing acting through Ago2 serine-387 phosphorylation mediated by the p38 MAPK pathway.
Mesh Terms:
Amino Acid Sequence, Anthracenes, Argonaute Proteins, Arsenites, Blotting, Western, Cell Line, Eukaryotic Initiation Factor-2, Flavonoids, Glutathione Transferase, Humans, Imidazoles, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, Mass Spectrometry, Microscopy, Confocal, Mitogen-Activated Protein Kinase Kinases, Molecular Sequence Data, Mutation, Phosphorylation, Protein-Serine-Threonine Kinases, Pyridines, Recombinant Proteins, Sequence Homology, Amino Acid, Serine, Sodium Compounds, p38 Mitogen-Activated Protein Kinases
Biochem. J.
Date: Aug. 01, 2008
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