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多瘤病毒中T抗原转化细胞中的磷脂酰肌醇代谢

Phosphatidylinositol metabolism in cells transformed by polyomavirus middle T antigen.

作者信息

Ulug E T, Hawkins P T, Hanley M R, Courtneidge S A

机构信息

Differentiation Programme, European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany.

出版信息

J Virol. 1990 Aug;64(8):3895-904. doi: 10.1128/JVI.64.8.3895-3904.1990.

DOI:10.1128/JVI.64.8.3895-3904.1990
PMID:2164601
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC249685/
Abstract

Associated with the middle T antigen of polyomavirus is a novel phosphatidylinositol (PtdIns) kinase activity which phosphorylates PtdIns at the D-3 position of the inositol ring. We have undertaken an analysis of myo-[3H]inositol-containing compounds in a panel of NIH 3T3 cell lines stably transfected with transforming and nontransforming middle T antigen mutants. All cell lines from which PtdIns 3-kinase activity coprecipitated with middle T antigen exhibited modestly elevated levels of PtdIns(3)P and compounds with predicted PtdIns(3,4)P2 and PtdIns(3,4,5)P3 structures. Complex formation between middle T antigen and PtdIns 3-kinase correlated not with an increase in total inositol phosphate levels but rather with elevated levels of InsP2 and InsP4. A specific increase in the level of an InsP2 species which comigrated in high-pressure liquid chromatography analysis with Ins(3,4)P2 was observed. These results suggest that association of the polyomavirus middle T antigen with PtdIns 3-kinase activates a distinct inositol metabolic pathway.

摘要

多瘤病毒的中间T抗原与一种新型磷脂酰肌醇(PtdIns)激酶活性相关,该活性可使肌醇环D-3位的PtdIns磷酸化。我们对一组稳定转染了转化型和非转化型中间T抗原突变体的NIH 3T3细胞系中含肌醇-[3H]的化合物进行了分析。所有PtdIns 3激酶活性与中间T抗原共沉淀的细胞系,其PtdIns(3)P以及具有预测的PtdIns(3,4)P2和PtdIns(3,4,5)P3结构的化合物水平均适度升高。中间T抗原与PtdIns 3激酶之间的复合物形成与总肌醇磷酸水平的增加无关,而是与InsP2和InsP4水平的升高有关。在高压液相色谱分析中观察到一种与Ins(3,4)P2共迁移的InsP2种类水平有特异性增加。这些结果表明,多瘤病毒中间T抗原与PtdIns 3激酶的结合激活了一条独特的肌醇代谢途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc78/249685/b2a3714ca99e/jvirol00063-0346-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc78/249685/b2a3714ca99e/jvirol00063-0346-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc78/249685/b2a3714ca99e/jvirol00063-0346-a.jpg

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Phosphotyrosine-containing proteins isolated by affinity chromatography with antibodies to a synthetic hapten.通过与合成半抗原抗体进行亲和层析分离得到的含磷酸酪氨酸的蛋白质。
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L-myo-inositol 1,4,5,6-tetrakisphosphate is present in both mammalian and avian cells.L-肌醇1,4,5,6-四磷酸存在于哺乳动物和鸟类细胞中。
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