LIF- and IL-6-induced acetylation of STAT3 at Lys-685 through PI3K/Akt activation

Norihiko Ohbayashi; Osamu Ikeda; Naohisa Taira; Yu Yamamoto; Ryuta Muromoto; Yuichi Sekine; Kenji Sugiyama; Tsutomu Honjoh; Tadashi Matsuda

doi:10.1248/bpb.30.1860

LIF- and IL-6-induced acetylation of STAT3 at Lys-685 through PI3K/Akt activation

Biol Pharm Bull. 2007 Oct;30(10):1860-4. doi: 10.1248/bpb.30.1860.

Authors

Norihiko Ohbayashi¹, Osamu Ikeda, Naohisa Taira, Yu Yamamoto, Ryuta Muromoto, Yuichi Sekine, Kenji Sugiyama, Tsutomu Honjoh, Tadashi Matsuda

Affiliation

¹ Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Kita-ku, Sapporo, Japan.

PMID: 17917251
DOI: 10.1248/bpb.30.1860

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylation / drug effects
Antibodies, Blocking / pharmacology
Blotting, Western
Cell Line
Chromones / pharmacology
Enzyme Activation / drug effects
Enzyme Inhibitors / pharmacology
Humans
Immunoprecipitation
Indicators and Reagents
Interleukin-6 / pharmacology*
Leukemia Inhibitory Factor / pharmacology*
Luciferases / genetics
Lysine / metabolism*
Morpholines / pharmacology
Oncogene Protein v-akt / drug effects
Oncogene Protein v-akt / metabolism*
Phosphatidylinositol 3-Kinases / drug effects
Phosphatidylinositol 3-Kinases / metabolism*
Phosphoinositide-3 Kinase Inhibitors
STAT3 Transcription Factor / metabolism*
Signal Transduction / drug effects
Transfection

Substances

Antibodies, Blocking
Chromones
Enzyme Inhibitors
Indicators and Reagents
Interleukin-6
Leukemia Inhibitory Factor
Morpholines
Phosphoinositide-3 Kinase Inhibitors
STAT3 Transcription Factor
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Luciferases
Oncogene Protein v-akt
Lysine