Regulation of c-Jun NH2-terminal kinases in isolated canine gastric parietal cells.
Regulation of c-Jun NH2-terminal kinases in isolated canine gastric parietal cells.
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离体犬胃壁细胞中 c-Jun NH2 末端激酶的调节。
DOI：
10.1152/ajpgi.1998.275.4.g740
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Todisco,A
中科院分区：
文献类型：
--
作者：
Nagahara,A;Wang,L;DelValle,J;Todisco,A
C-Jun氨基末端激酶(JNKs)是一种可被多种细胞外信号激活的蛋白激酶。本研究探讨JNKs在犬胃壁细胞中的表达及调控。用识别JNK1和较少识别JNK2的抗体对高纯度(>；95%)壁细胞裂解产物进行Western印迹分析，发现分别存在两条46和54 kDa的条带。用免疫沉淀法和凝胶内激酶法测定JNK1活性。在所测试的不同试剂中，氨基甲胆碱是最有效的JNK1活性诱导剂，而组胺和表皮生长因子诱导的反应较弱。促炎症细胞因子肿瘤坏死因子-α刺激JNK1，但对细胞外信号调节蛋白2的诱导无影响，提示JNK1的激活可能是介导胃炎症反应的重要事件。卡巴胆碱的作用呈剂量和时间依赖关系，30min后刺激作用最强(4倍)，持续2 h，加入特异性蛋白激酶C抑制剂GF109203X不影响卡巴胆碱的刺激作用。细胞内钙离子螯合剂1，2-二(2-氨基苯氧基)乙烷-N，N，N‘，N’-四乙酸-AM对氨基甲胆碱诱导的JNK1活性的抑制作用达60%。胞内钙离子上升剂山茶素(1μM)可使JNK1活性增加3倍以上。Carbacol激活JNK1可诱导c-jun(蛋白)转录活性，并刺激壁细胞c-jun的mRNA含量。综上所述，我们的研究结果表明，卡巴胆碱通过细胞内钙离子依赖、PKC非依赖的途径诱导胃壁细胞JNK活性，从而通过c-jun的磷酸化和转录激活来诱导c-jun基因的表达。
c-Jun NH2-terminal kinases (JNKs) are protein kinases that are activated by a wide variety of extracellular signals. This study investigated the expression and regulation of JNKs in isolated gastric canine parietal cells. Western blot analysis of cell lysates from highly purified (>95%) parietal cells with an antibody recognizing JNK1 and to a lesser degree JNK2 revealed the presence of two bands of 46 and 54 kDa, respectively. JNK1 activity was quantitated by immunoprecipitation and in-gel kinase assays. Of the different agents tested, carbachol was the most potent inducer of JNK1 activity, whereas histamine and epidermal growth factor induced weaker responses. The proinflammatory cytokine tumor necrosis factor-α stimulated JNK1 but had no effect on extracellular signal-regulated kinase (ERK2) induction, suggesting that activation of JNK1 might represent an important event in mediation of the inflammatory response in the stomach. The action of carbachol was dose (0.1–100 μM) and time dependent, with a maximal stimulatory effect (fourfold) detected after 30 min of incubation and sustained for 2 h. Addition of the specific protein kinase C (PKC) inhibitor GF109203X did not affect the stimulatory action of carbachol. The intracellular Ca2+chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid-AM inhibited carbachol induction of JNK1 activity by 60%. Thapsigargin (1 μM), an intracellular Ca2+-rising agent, induced JNK1 activity more than threefold. Carbachol activation of JNK1 resulted in induction of c-Jun (protein) transcriptional activity and in stimulation of parietal cell mRNA content of c-jun. In conclusion, our data indicate that carbachol induces JNK activity in gastric parietal cells via intracellular Ca2+-dependent, PKC-independent pathways, leading to induction of c-jungene expression via phosphorylation and transcriptional activation of c-Jun.
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DOI：
10.1152/ajpgi.1994.267.2.g245
发表时间：
1994
期刊：
The American journal of physiology
影响因子：
--
作者：
Todisco,A;Campbell,V;Dickinson,CJ;DelValle,J;Yamada,T
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GUAN, KL;DIXON, JE
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影响因子：
56.9
作者：
J. Marx
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[35] c-Jun激酶的分析方法
DOI：
--
发表时间：
1995
期刊：
影响因子：
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作者：
J. Westwick;D. Brenner
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壁细胞 MAP 激酶：多种激活途径。
DOI：
10.1152/ajpgi.1996.271.4.g640
发表时间：
1996
期刊：
The American journal of physiology
影响因子：
--
作者：
K. Nakamura;C. Zhou;J. Parente;C. Chew
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C. Chew