A selective PIKfyve inhibitor blocks PtdIns(3,5)P(2) production and disrupts endomembrane transport and retroviral budding.
A selective PIKfyve inhibitor blocks PtdIns(3,5)P(2) production and disrupts endomembrane transport and retroviral budding.
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DOI：
10.1038/sj.embor.7401155
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发表时间：
2008-02
期刊：
影响因子：
7.7
通讯作者：
Parker, Peter J.
中科院分区：
文献类型：
--
作者：
Jefferies, Harold B. J.;Cooke, Frank T.;Jat, Parmjit;Boucheron, Christine;Koizumi, Tomonobu;Hayakawa, Masahiko;Kaizawa, Hiroyuki;Ohishi, Takahide;Workman, Paul;Waterfield, Michael D.;Parker, Peter J.
磷酸肌醇在细胞控制中具有关键作用，其中许多已经通过使用小分子抑制剂建立。在这里，我们描述了YM 201636，一种有效的哺乳动物III类磷脂酰肌醇磷酸激酶PIKfyve的抑制剂，它合成磷脂酰肌醇3，5-二磷酸。用YM 201636急性处理细胞显示PIKfyve途径参与内体转运的分选，抑制导致晚期内体隔室的积累和逆转录病毒出口的阻断。通过使用针对靶点的短干扰RNA以及通过用耐药酵母直向同源物Fab 1拯救来显示抑制剂特异性。我们得出结论，磷脂酰肌醇3，5-二磷酸途径是内体形成不可或缺的，决定形态和货物流量。
Phosphoinositides have crucial roles in cellular controls, many of which have been established through the use of small-molecule inhibitors. Here, we describe YM201636, a potent inhibitor of the mammalian class III phosphatidylinositol phosphate kinase PIKfyve, which synthesizes phosphatidylinositol 3,5-bisphosphate. Acute treatment of cells with YM201636 shows that the PIKfyve pathway is involved in the sorting of endosomal transport, with inhibition leading to the accumulation of a late endosomal compartment and blockade of retroviral exit. Inhibitor specificity is shown by the use of short interfering RNA against the target, as well as by rescue with the drug-resistant yeast orthologue Fab1. We concluded that the phosphatidylinositol 3,5-bisphosphate pathway is integral to endosome formation, determining morphology and cargo flux.
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影响因子：
4
作者：
Berwick, DC;Dell, GC;Tavaré, JM
通讯作者：
Tavaré, JM
DOI：
10.1083/jcb.131.6.1715
发表时间：
1995-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Nakamura N;Rabouille C;Watson R;Nilsson T;Hui N;Slusarewicz P;Kreis TE;Warren G
通讯作者：
Warren G
DOI：
10.1073/pnas.92.2.522
发表时间：
1995-01-17
影响因子：
11.1
作者：
SAPPERSTEIN, SK;WALTER, DM;WATERS, MG
通讯作者：
WATERS, MG
影响因子：
3.3
作者：
Ikonomov, OC;Sbrissa, D;Shisheva, A
通讯作者：
Shisheva, A
影响因子：
4.8
作者：
McEwen, RK;Dove, SK;Michell, RH
通讯作者：
Michell, RH