Activation of Jun kinase is an early event in hepatic regeneration.
Activation of Jun kinase is an early event in hepatic regeneration.
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DOI：
10.1172/jci117730
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发表时间：
1995-02
期刊：
影响因子：
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通讯作者：
J. Westwick;C. Weitzel;H. Leffert;D. Brenner
中科院分区：
文献类型：
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作者：
J. Westwick;C. Weitzel;H. Leffert;D. Brenner
部分肝切除术（PH）后的代偿性肝再生取决于切除范围。本研究分析了AP-1转录因子c-Jun在肝再生过程中的调控。假手术、三分之一PH和三分之二PH后c-jun mRNA水平逐渐增加。还观察到 AP-1 结合活性随之增加。 c-Jun 蛋白是静止和早期再生肝脏中 AP-1 复合物的主要成分。 c-Jun 核激酶 (JNK) 磷酸化 c-Jun 蛋白的激活结构域，其活性在三分之一 PH 后显着增强。 JNK1 或免疫相关激酶是 PH 后刺激的 JNK 活性的组成部分。当成年大鼠肝细胞的原代培养物与表皮生长因子或转化生长因子-α 一起孵育时，AP-1 转录活性增加，c-Jun 蛋白的激活结构域进一步增强。增殖培养肝细胞中内源性 c-Jun 蛋白的磷酸肽图谱表明 c-Jun 激活结构域的磷酸化。结合这些体内和培养研究的结果，我们得出结论，三分之一 PH 的最小刺激会激活 JNK，从而磷酸化肝细胞中的 c-Jun 激活结构域，从而导致 AP-1 依赖性基因的转录增强。
Compensatory hepatic regeneration after partial hepatectomy (PH) is dependent upon the extent of resection. This study analyzes the regulation of the AP-1 transcription factor c-Jun during hepatic regeneration. There is a progressive increase in c-jun mRNA levels after sham operation, one-third PH, and two-thirds PH. A concomitant increase in AP-1 binding activity is also observed. The c-Jun protein is a major constituent of the AP-1 complex in quiescent and early regenerating liver. The activity of c-Jun nuclear kinase (JNK), which phosphorylates the activation domain of the c-Jun protein, is markedly stimulated after one-third PH. JNK1 or an immunologically related kinase is a constituent of this stimulated JNK activity after PH. When primary cultures of adult rat hepatocytes are incubated with epidermal growth factor or transforming growth factor-alpha, AP-1 transcriptional activity is increased and the activation domain of the c-Jun protein is further potentiated. Phosphopeptide mapping of the endogenous c-Jun protein in proliferating cultured hepatocytes demonstrates phosphorylation of the c-Jun activation domain. Combining the results of these in vivo and culture studies, we conclude that the minimal stimulation of one-third PH activates JNK, which phosphorylates the c-Jun activation domain in hepatocytes, resulting in enhanced transcription of AP-1-dependent genes.