The human homologue of yeast ArgRIII protein is an inositol phosphate multikinase with predominantly nuclear localization

被引:78
作者
Nalaskowski, MM [1 ]
Deschermeier, C [1 ]
Fanick, W [1 ]
Mayr, GW [1 ]
机构
[1] Univ Hamburg, Klinikum Eppendorf, Inst Med Biochem & Mol Biol, Abt Zellulaere Signaltransdukt, D-20246 Hamburg, Germany
关键词
Arg(82); inositol 1,3,4,5,6-pentakisphosphate; nuclear localization signal; nucleus;
D O I
10.1042/BJ20020327
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:549 / 556
页数:8
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