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h-sgk丝氨酸-苏氨酸蛋白激酶作为p38/丝裂原活化蛋白激酶通路在人肝癌细胞系HepG2中的转录靶点。

h-sgk serine-threonine protein kinase as transcriptional target of p38/MAP kinase pathway in HepG2 human hepatoma cells.

作者信息

Waldegger S, Gabrysch S, Barth P, Fillon S, Lang F

机构信息

Institut für Physiologie I, Gmelinstr. 5, D-72076 Tübingen, Germany.

出版信息

Cell Physiol Biochem. 2000;10(4):203-8. doi: 10.1159/000016351.

DOI:10.1159/000016351
PMID:11093030
Abstract

The human serum and glucocorticoid dependent serine/threonine kinase h-sgk has previously been discovered as cell volume regulated gene. The present study has been performed to elucidate the involvement of p38-kinase in the transcriptional control of h-sgk by osmotic cell shrinkage. The p38-kinase has previously been cloned as the mammalian homologue of HOG1 kinase, which constitutes a part of the osmosensor in the yeast Saccharomyces cerevisiae. Phosphorylated (active) p38-kinase has been estimated with Western blotting, transcription of hsgk using Northern blotting. Both, increase of extracellular NaCl concentration by 50 mmol/l and addition of 10 micromol/l anisomycin increase phosphorylation of the p38-kinase within 5 to 10 minutes. h-sgk transcription is upregulated by addition of 50 mmol/l NaCl and by anisomycin (10 micromol/l), effects completely inhibited by the specific p38-kinase inhibitor, SB 203580 (10 micromol/l). In conclusion, the stimulation of h-sgk transcription by osmotic cell shrinkage is mediated by p38-kinase.

摘要

人血清和糖皮质激素依赖性丝氨酸/苏氨酸激酶h-sgk先前已被发现是一种细胞体积调节基因。本研究旨在阐明p38激酶在渗透细胞收缩对h-sgk转录调控中的作用。p38激酶先前已被克隆为HOG1激酶的哺乳动物同源物,HOG1激酶是酿酒酵母渗透压感受器的一部分。通过蛋白质免疫印迹法估计磷酸化(活性)p38激酶,使用Northern印迹法检测hsgk的转录。细胞外NaCl浓度增加50 mmol/l以及添加10 μmol/l茴香霉素均可在5至10分钟内增加p38激酶的磷酸化。添加50 mmol/l NaCl和茴香霉素(10 μmol/l)可上调h-sgk转录,而特异性p38激酶抑制剂SB 203580(10 μmol/l)可完全抑制这些作用。总之,渗透细胞收缩对h-sgk转录的刺激是由p38激酶介导的。

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