LIF- and IL-6-induced acetylation of STAT3 at Lys-685 through PI3K/Akt activation.
LIF- and IL-6-induced acetylation of STAT3 at Lys-685 through PI3K/Akt activation.
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DOI：
10.1248/bpb.30.1860
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发表时间：
2007-10
影响因子：
2
通讯作者：
N. Ohbayashi;O. Ikeda;N. Taira;Yukimi Yamamoto;R. Muromoto;Y. Sekine;K. Sugiyama;T. Honjoh;T. Matsuda
中科院分区：
文献类型：
--
作者：
N. Ohbayashi;O. Ikeda;N. Taira;Yukimi Yamamoto;R. Muromoto;Y. Sekine;K. Sugiyama;T. Honjoh;T. Matsuda
信号转导子和转录激活子3（STAT 3）是细胞因子和生长因子通过酪氨酸或丝氨酸磷酸化、二聚化和核转位等途径激活的，在许多生理过程中发挥重要作用。最近的一项研究表明，通过使用乙酰化赖氨酸的抗体和具有Lys-685-to-Arg取代的STAT 3突变体，STAT 3通过组蛋白乙酰转移酶p300在Lys-685处乙酰化，并且在Lys-685处的乙酰化对于STAT 3活化至关重要。在本研究中，我们创建了一个乙酰化特异性抗体，针对STAT 3的乙酰化在Lys-685，并发现白血病抑制因子（LIF）或白细胞介素（IL）-6诱导STAT 3的乙酰化在293 T和Hep 3B细胞中的Lys-685。此外，STAT 3在Lys-685处的乙酰化被PI 3 K抑制剂LY 294002或显性负性Akt抑制。总之，我们的研究结果表明，内源性STAT 3是乙酰化的赖氨酸-685由LIF或IL-6通过PI 3 K/Akt激活。
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.