INDUCTION AND DOWN-REGULATION OF PLK, A HUMAN SERINE/THREONINE KINASE EXPRESSED IN PROLIFERATING CELLS AND TUMORS
INDUCTION AND DOWN-REGULATION OF PLK, A HUMAN SERINE/THREONINE KINASE EXPRESSED IN PROLIFERATING CELLS AND TUMORS
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DOI：
10.1073/pnas.91.5.1736
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发表时间：
1994-03-01
影响因子：
11.1
通讯作者：
STREBHARDT, K
中科院分区：
文献类型：
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作者：
HOLTRICH, U;WOLF, G;STREBHARDT, K
我们已经确定了编码人类对应的小鼠基因Plk （polo样激酶）的cDNA的核苷酸序列。人类基因PLK的序列预测了603aa的丝氨酸/苏氨酸激酶。PLK mRNA的表达似乎与细胞的有丝分裂活性密切相关。静息时外周淋巴细胞完全不表达该基因。当原代T细胞被植物血凝素激活时，在2-3天内产生高水平的PLK转录本。在某些情况下，在这些细胞中加入白细胞介素2进一步增加了PLK mRNA的表达。相比之下，在培养条件下不分裂的人外周巨噬细胞的原代培养物很少或没有PLK mRNA。细菌脂多糖（巨噬细胞中几种细胞因子的诱导剂）对这些细胞的刺激完全消除了PLK mRNA的表达。与PLK mRNA在有丝分裂活跃细胞中的表达功能一致的是，我们发现6个永生化细胞系表达了该基因。在A-431表皮样癌细胞中，血清饥饿后表达下调，再次加入血清后表达增强。各种来源的肿瘤（肺、结肠、胃、平滑肌、食道以及非霍奇金淋巴瘤）在大约80%的研究样本中表达高水平的PLK转录本，而PLK mRNA在周围组织中缺失，除了结肠。唯一观察到PLK mRNA表达的正常组织是结肠和胎盘，两者都是有丝分裂活跃的。在正常成人肺、脑、兽、肝、肾、骨骼肌和胰腺中未发现PLK转录本。在用植物血凝素和环己亚胺处理的淋巴细胞的RNA进行的Northern blot实验中，未检测到PLK转录物，这表明PLK不是早期生长反应基因。
We have identified the nucleotide sequence of the cDNA encoding the human counterpart of the mouse gene Plk (polo-like kinase). The sequence of the human gene, PLK, predicts a serine/threonine kinase of 603 aa. Expression of PLK mRNA appeared to be strongly correlated with the mitotic activity of cells. Resting peripheral lymphocytes did not express the gene at all. When primary T cells were activated by phytohemagglutinin, a high level of PLK transcripts resulted within 2-3 days. In some cases, addition of interleukin 2 to these cells increased the expression of PLK mRNA further. In contrast, primary cultures of human peripheral macrophages, which were not dividing under the culture conditions applied, showed very little or no PLK mRNA. Stimulation of these cells by bacterial lipopolysaccharide, an inducer of several cytokines in macrophages, totally abrogated the expression of PLK mRNA. In line with a function of PLK mRNA expression in mitotically active cells is our finding that six immortalized cell lines examined expressed the gene. In A-431 epidermoid carcinoma cells this expression was down-regulated by serum starvation and enhanced after serum was added again. Tumors of various origin (lung, colon, stomach, smooth muscle, and esophagus as well as non-Hodgkin lymphomas) expressed high levels of PLK transcripts in about 80% of the samples studied, whereas PLK mRNA was absent in surrounding tissue, except for colon. The only normal tissues where PLK mRNA expression was observed were colon and placenta, both known to be mitotically active. No PLK transcripts were found in normal adult lung, brain, beast, liver, kidney, skeletal muscle, and pancreas. In Northern blot experiments with RNA from lymphocytes which were treated with phytohemagglutinin and cycloheximide, PLK transcripts were not detectable, suggesting that PLK is not an early growth-response gene.