Phosphorylation of threonine-265 in Zipper-interacting protein kinase plays an important role in its activity and is induced by IL-6 family cytokines.
Zipper-interacting protein kinase (ZIPK) is a widely expressed serine/threonine kinase that has been implicated in cell death and transcriptional regulation, but its mechanism of regulation remains unknown. Here, we identified threonine-265 (Thr265) in ZIPK as a major autophosphorylation site. Mutational analyses revealed that autophosphorylation of Thr265 were essential for its full catalytic activity toward an exogenous substrate as well as for cell death induction. Furthermore, leukemia inhibitory factor (LIF) stimulated Thr265 phosphorylation of ZIPK, thereby leading to phosphorylation and activation of signal transducer and activator of transcription (STAT3). Taken together, our findings demonstrate that ZIPK is positively regulated through Thr265 phosphorylation and that this phosphorylation is essential for its function.
Sato
Noriko
N
Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku Kita 12 Nishi 6, Sapporo 060-0812, Japan.
Kamada
Nobuyuki
N
Muromoto
Ryuta
R
Kawai
Taro
T
Sugiyama
Kenji
K
Watanabe
Tadashi
T
Imoto
Seiyu
S
Sekine
Yuichi
Y
Ohbayashi
Norihiko
N
Ishida
Masato
M
Akira
Shizuo
S
Matsuda
Tadashi
T
D000818:Animals; D006367:HeLa Cells; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013912:Threonine / Q000378:metabolism*
D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D013912:Threonine; D020930:MAP Kinase Kinase Kinases; C090757:mitogen-activated protein kinase kinase kinase 12