Phosphorylation of threonine-265 in Zipper-interacting protein kinase plays an important role in its activity and is induced by IL-6 family cytokines
Phosphorylation of threonine-265 in Zipper-interacting protein kinase plays an important role in its activity and is induced by IL-6 family cytokines
复制标题
DOI：
10.1016/j.imlet.2005.10.015
复制
发表时间：
2006-03-15
影响因子：
4.4
通讯作者：
Matsuda, T
中科院分区：
文献类型：
--
作者：
Sato, N;Kamada, N;Matsuda, T
ZIPK是一种广泛表达的丝氨酸/苏氨酸激酶，与细胞死亡和转录调控有关，但其调控机制尚不清楚。在这里，我们确定了ZIPK中的苏氨酸-265 （Thr265）是一个主要的自磷酸化位点。突变分析显示，Thr265的自磷酸化对于其对外源底物的充分催化活性以及诱导细胞死亡至关重要。此外，白血病抑制因子（LIF）刺激Thr265磷酸化ZIPK，从而导致信号换能器和转录激活因子（STAT3）的磷酸化和激活。综上所述，我们的研究结果表明，ZIPK通过Thr265磷酸化受到正调控，而这种磷酸化对其功能至关重要。(C) 2005 Elsevier B.V.版权所有
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. (C) 2005 Elsevier B.V. All rights reserved.