The human homologue of yeast ArgRIII protein is an inositol phosphate multikinase with predominantly nuclear localization
The human homologue of yeast ArgRIII protein is an inositol phosphate multikinase with predominantly nuclear localization
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DOI：
10.1042/bj20020327
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发表时间：
2002-09-01
影响因子：
4.1
通讯作者：
Mayr, GW
中科院分区：
文献类型：
--
作者：
Nalaskowski, MM;Deschermeier, C;Mayr, GW
转录调节因子ArgRIII在酵母中参与精氨酸代谢的几个基因的表达中的功能已经被很好地研究。先前报道它也是肌醇磷酸多激酶和mRNA输出途径的重要因子[由Shears（2000）Bioessays 22，786-789综述]。在.本研究克隆了人磷酸肌醇多激酶（IPMK）的全长cDNA。该蛋白的计算分子量为47.219 kDa。功能上重要的基序[磷酸肌醇结合位点、ATP结合位点、催化上重要的SSLL（Ser-Ser-Leu-Leu）结构域]在人IPMK和酵母ArgRIII之间是保守的。细菌表达的蛋白质表现出类似于酵母ArgRIII的磷酸肌醇多激酶活性。Ins（1，4，5）P-3在位置3和6处被磷酸化直至Ins（1，3，4，5，6）P-5。与荧光蛋白标签融合的人IPMK在哺乳动物细胞中瞬时表达时主要定位于细胞核中。蛋白质C末端的一个基本簇积极参与核靶向。这些发现与哺乳动物细胞中的核肌醇磷酸信号传导和磷酸化途径的概念一致。
The function of the transcription regulator ArgRIII in the expression of several genes involved in the metabolism of arginine in yeast has been well studied. It was previously reported that it is also an inositol phosphate multikinase and an important factor of the mRNA export pathway [reviewed by Shears (2000) Bioessays 22, 786-789]. In the. present study we report the cloning of a full-length 1248-bp cDNA encoding a human inositol phosphate multikinase (IPMK). This protein has a calculated molecular mass of 47.219 kDa. Functionally important motifs [inositol phosphate-binding site, ATP-binding site, catalytically important SSLL (Ser-Ser-Leu-Leu) domain] are conserved between the human IPMK and yeast ArgRIII. Bacterially expressed protein demonstrated an inositol phosphate multikinase activity similar to that of yeast ArgRIII. Ins(1,4,5)P-3 is phosphorylated at positions 3 and 6 up to Ins(1,3,4,5,6)P-5. The human IPMK fused with a fluorescent protein tag is localized predominantly in the nucleus when transiently expressed in mammalian cells. A basic cluster in the protein's C-terminus is positively involved in nuclear targeting. These findings are consistent with the concept of a nuclear inositol phosphate signalling and phosphorylation pathway in mammalian cells.