Nuclear targeting of the beta isoform of type II phosphatidylinositol phosphate kinase (phosphatidylinositol 5-phosphate 4-kinase) by its alpha-helix 7.

Nuclear targeting of the beta isoform of type II phosphatidylinositol phosphate kinase (phosphatidylinositol 5-phosphate 4-kinase) by its alpha-helix 7.
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II 型磷脂酰肌醇磷酸激酶(磷脂酰肌醇 5-磷酸 4-激酶)的 β 亚型通过其 α 螺旋 7 进行核靶向。

DOI:
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发表时间:
2000
影响因子:
4.1
通讯作者:
R. F. Irvine
R. F. Irvine
中科院分区:
生物学3区
文献类型:
--
作者:
A. Ciruela;K. Hinchliffe;N. Divecha;R. F. Irvine

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最近发现II型磷脂酰肌醇磷酸激酶(PIPkins)主要是磷脂酰肌醇5-磷酸4-激酶,其生理作用仍不清楚。我们之前已经证明 II 型 PIPkin [亚型未知] 部分位于细胞核中 [Divecha, Rhee, Letcher 和 Irvine (1993) Biochem. J. 289, 617-620],在这里,我们通过用绿色荧光蛋白标记的 II 型 PIPkin 转染 HeLa 细胞,表明这可能是 IIbeta 亚型。 IIbeta PIPkin 没有明显的核定位序列,对嵌合体以及 α(胞质)和 β PIPkin 突变体的定位的详细分析表明,核定位需要存在 17 个氨基酸长度的 α 螺旋(α 螺旋 7),该螺旋是 β 异构体特有的,并且该螺旋必须完整存在,并且具有精确的方向。这类似于 HIV 蛋白 Vpr 的核靶向,因此 IIbeta PIPkin 显然是使用相同机制的真核蛋白的第一个例子。
Type II phosphatidylinositol phosphate kinases (PIPkins) have recently been found to be primarily phosphatidylinositol 5-phosphate 4-kinases, and their physiological role remains unclear. We have previously shown that a Type II PIPkin [isoform(s) unknown], is localized partly in the nucleus [Divecha, Rhee, Letcher and Irvine (1993) Biochem. J. 289, 617-620], and here we show, by transfection of HeLa cells with green-fluorescent-protein-tagged Type II PIPkins, that this is likely to be the Type IIbeta isoform. Type IIbeta PIPkin has no obvious nuclear localization sequence, and a detailed analysis of the localization of chimaeras and mutants of the alpha (cytosolic) and beta PIPkins shows that the nuclear localization requires the presence of a 17-amino-acid length of alpha-helix (alpha-helix 7) that is specific to the beta isoform, and that this helix must be present in its entirety, with a precise orientation. This resembles the nuclear targeting of the HIV protein Vpr, and Type IIbeta PIPkin is apparently therefore the first example of a eukaryotic protein that uses the same mechanism.