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首页> 外文期刊>Molecular and Cellular Biology >Lipopolysaccharide-induced NF-kappa B activation in mouse 70Z/3 pre-B lymphocytes is inhibited by mevinolin and 5'-methylthioadenosine: roles of protein isoprenylation and carboxyl methylation reactions.
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Lipopolysaccharide-induced NF-kappa B activation in mouse 70Z/3 pre-B lymphocytes is inhibited by mevinolin and 5'-methylthioadenosine: roles of protein isoprenylation and carboxyl methylation reactions.

机译：mevinolin和5'-methylthioadenosine抑制小鼠70Z / 3 pre-B淋巴细胞中脂多糖诱导的NF-κB活化：蛋白质异戊二烯化和羧基甲基化反应的作用。

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摘要

We show that both the lipopolysaccharide (LPS)-induced activation of NF-kappa DNA binding and kappa gene expression are blocked by treating murine pre-B lymphocyte 70Z/3 cells with 5'-methylthioadenosine (MTA), an inhibitor of several S-adenosylmethionine-dependent methylation reactions. We further show that the LPS-induced incorporation of radioactivity from [methyl-3H]methionine into methyl ester-like linkages on a group of membrane polypeptides is also inhibited by MTA treatment, suggesting the involvement of protein methylation reactions in the LPS signal transduction pathway. We also find that NF-kappa B and kappa gene activation in LPS-treated 70Z/3 cells is blocked by mevinolin, an inhibitor that prevents protein isoprenylation. Interestingly, mevinolin-treated cells also exhibited a marked reduction in the methylation of membrane proteins. Neither MTA nor mevinolin significantly inhibited NF-kappa B activation by phorbol myristate acetate, suggesting that these agents act early in signal transduction. These results provide the first evidence that carboxyl methylated and/or isoprenylated proteins play an essential role in the LPS-signaling pathway.
机译：我们显示，脂多糖（LPS）诱导的NF-κBDNA结合激活和κ基因表达均通过用5'-甲基硫代腺苷（MTA）（几种S-的抑制剂）处理鼠前B淋巴细胞70Z / 3细胞而被阻断腺苷甲硫氨酸依赖性甲基化反应。我们进一步表明，MTA处理还可以抑制LPS诱导的[甲基-3H]蛋氨酸放射性结合到一组膜多肽上的甲酯样连接中，这提示LPS信号转导途径中涉及蛋白质甲基化反应。我们还发现，LPS处理的70Z / 3细胞中的NF-κB和κ基因激活被mevinolin阻止，后者是一种防止蛋白质异戊二烯化的抑制剂。有趣的是，用美维诺林处理的细胞还表现出膜蛋白甲基化的显着减少。 MTA或mevinolin都不能通过肉豆蔻酸乙酸佛波酯显着抑制NF-κB的活化，表明这些试剂在信号转导的早期起作用。这些结果提供了第一个证据，即羧甲基化和/或异戊二烯基化的蛋白质在LPS信号通路中起着至关重要的作用。

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