Deactivation of STAT6 through serine 707 phosphorylation by JNK.
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-1β (IL-1β). 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-1β and IL-4 signals.
Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 611-0011, Japan.
Takashi
T
Shirakawa
Yoshinori
Y
Kawazoe
Tomoko
T
Tsujikawa
Dongju
D
Jung
Shin-ichi
S
Sato
Motonari
M
Uesugi
D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D053583:Interleukin-1beta; D015847:Interleukin-4; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology*; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D013312:Stress, Physiological; D014158:Transcription, Genetic
D053583:Interleukin-1beta; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015847:Interleukin-4; D012694:Serine; D004247:DNA; D048031:JNK Mitogen-Activated Protein Kinases