LIF- and IL-6-induced acetylation of STAT3 at Lys-685 through PI3K/Akt activation.
Signal transducer and activator of transcription 3 (STAT3), which mediates biological actions in many physiological processes, is activated by cytokines and growth factors via specific tyrosine or serine phosphorylation, dimerization and nuclear translocation. A recent study has demonstrated, by using antibody to acetylated lysine, and a STAT3 mutant with Lys-685-to-Arg substitution, that STAT3 is acetylated at Lys-685 by histone acetyltransferase p300, and that acetylation at Lys-685 is critical for STAT3 activation. In the present study, we created an acetyl-specific antibody against STAT3 acetylated at Lys-685, and found that leukemia inhibitory factor (LIF) or interleukin (IL)-6 induced acetylation of STAT3 at Lys-685 in 293T and Hep3B cells. Moreover, acetylation of STAT3 at Lys-685 was suppressed by PI3K inhibitor LY294002, or a dominant negative Akt. Taken together, our findings demonstrate that endogenous STAT3 is acetylated at Lys-685 by LIF or IL-6 through PI3K/Akt activation.
Ohbayashi
Norihiko
N
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Kita-ku, Sapporo, Japan.
Ikeda
Osamu
O
Taira
Naohisa
N
Yamamoto
Yu
Y
Muromoto
Ryuta
R
Sekine
Yuichi
Y
Sugiyama
Kenji
K
Honjoh
Tsutomu
T
Matsuda
Tadashi
T
D000107:Acetylation / Q000187:drug effects; D019138:Antibodies, Blocking / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D047468:Immunoprecipitation; D007202:Indicators and Reagents; D015850:Interleukin-6 / Q000494:pharmacology*; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology*; D008156:Luciferases / Q000235:genetics; D008239:Lysine / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
D019138:Antibodies, Blocking; D002867:Chromones; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008156:Luciferases; D008239:Lysine; D009025:Morpholines; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D050796:STAT3 Transcription Factor; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one