Deactivation of STAT6 through Serine 707 Phosphorylation by JNK
Deactivation of STAT6 through Serine 707 Phosphorylation by JNK
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DOI：
10.1074/jbc.m110.168435
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发表时间：
2011-02-04
影响因子：
4.8
通讯作者：
Uesugi, Motonari
中科院分区：
文献类型：
--
作者：
Shirakawa, Takashi;Kawazoe, Yoshinori;Uesugi, Motonari
信号转导器和转录激活剂 6 (STAT6) 在免疫反应中发挥着关键作用，由白细胞介素 4 (IL-4) 激活。 STAT 家族成员的活性主要受酪氨酸磷酸化调节，也可能受丝氨酸磷酸化调节。在此，我们报告了先前未描述的 STAT6 丝氨酸磷酸化，该磷酸化由细胞应激或促炎细胞因子白细胞介素 1 β (IL-1 β) 激活。我们的分析表明 Ser-707 被 c-Jun N 末端激酶 (JNK) 磷酸化。磷酸化降低了 IL-4 刺激的 STAT6 的 DNA 结合能力，从而抑制 STAT6 响应基因的转录。 JNK 依赖性 Ser-707 磷酸化导致 STAT6 失活可能是控制 IL-1 β 和 IL-4 信号之间平衡的机制之一。
Signal transducer and activator of transcription 6 (STAT6), which plays a critical role in immune responses, is activated by interleukin-4 (IL-4). Activity of STAT family members is regulated primarily by tyrosine phosphorylations and possibly also by serine phosphorylations. Here, we report a previously undescribed serine phosphorylation of STAT6, which is activated by cell stress or by the pro-inflammatory cytokine, interleukin-1 beta (IL-1 beta). Our analyses suggest that Ser-707 is phosphorylated by c-Jun N-terminal kinase (JNK). Phosphorylation decreases the DNA binding ability of IL-4-stimulated STAT6, thereby inhibiting the transcription of STAT6-responsive genes. Inactivation of STAT6 by JNK-dependent Ser-707 phosphorylation may be one mechanism of controlling the balance between IL-1 beta and IL-4 signals.