Biol. Pharm. Bull. 30(10) 1860—1864 (2007)

is a member of the STAT protein family, and is mainly activated by the interleukin (IL)-6 family of cytokines, interferons, epidermal growth factor and leptin. Similar to other members of the STAT family, upon cytokine stimulation, STAT3 is tyrosine-phosphorylated at Tyr-705 by Janus kinases (Jaks), and is subsequently dimerized and translocated to the nucleus to activate its target genes. STAT3 is also phosphorylated at Ser-727 in response to cytokine stimulation. Phosphorylation of STAT3 at Ser-727 is required for the maximal transcriptional activation of STAT3. Ser-727 phosphorylation is also shown to increase STAT3 activity through association with other cofactors, such as p300. Recently, it has also been demonstrated that STAT3 is acetylated by oncostatin M (OSM) or interferon-a (IFN-a) stimulation. Furthermore, experiments using antibody to acetylated lysine, and a STAT3 mutant with a Lys-685-to-Arg substitution, have revealed that STAT3 is acetylated at Lys-685 by histone acetyltransferase p300, and its acetylation is critical for the formation of stable dimers required for transcriptional activation. In the present study, we created an acetyl-specific antibody against STAT3 acetylated at Lys-685, and found that leukemia inhibitory factor (LIF) and IL-6 induced acetylation of STAT3 at Lys-685. Furthermore, IL-6-induced acetylation at Lys-685 was suppressed by PI3K inhibitor, LY294002. Moreover, a dominant negative Akt inhibited acetylation of STAT3 at Lys-685 by p300. These results suggest that LIF or IL-6 mediates acetylation of STAT3 at Lys685 through activation of the PI3K/Akt signaling pathway.