A novel family of phosphatidylinositol 4-kinases conserved from yeast to humans
A novel family of phosphatidylinositol 4-kinases conserved from yeast to humans
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DOI：
10.1074/jbc.c000861200
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发表时间：
2001-03-16
影响因子：
4.8
通讯作者：
Albanesi, JP
中科院分区：
文献类型：
--
作者：
Barylko, B;Gerber, SH;Albanesi, JP
磷脂酰肌醇多磷酸（PIP）主要参与许多生物学过程，从细胞生长和肌动蛋白细胞骨架的组织到胞内和胞吐。磷脂酰肌醇在D-4位的磷酸化是PIP生物合成的重要步骤，似乎由两种生物化学上不同的酶催化。然而，这两种酶中只有一种被分子表征。我们现在描述一类新的磷脂酰肌醇4-激酶，可能对应于磷脂酰肌醇代谢中缺失的元素。这些激酶在进化上是高度保守的，但与先前表征的磷脂酰肌醇激酶无关，因此代表了一个新家族的创始成员。在细胞中广泛表达的新型磷脂酰肌醇4-激酶仅磷酸化磷脂酰肌醇，被腺苷有效抑制，但对渥曼青霉素或氧化苯胂不敏感。虽然它们缺乏明显的跨膜结构域，但它们通过棕榈酰化牢固地附着在膜上。我们的数据表明，独立的磷脂酰肌醇4-磷酸合成途径出现在进化过程中，可能允许严格的时间和空间控制生产的这一关键信号分子。
Phosphatidylinositolpolyphosphates (PIPs) are centrally involved in many biological processes, ranging from cell growth and organization of the actin cytoskeleton to endo- and exocytosis. Phosphorylation of phosphatidylinositol at the D-4 position, an essential step in the biosynthesis of PIPs, appears to be catalyzed by two biochemically distinct enzymes. However, only one of these two enzymes has been molecularly characterized. We now describe a novel class of phosphatidylinositol 4-kinases that probably corresponds to the missing element in phosphatidylinositol metabolism. These kinases are highly conserved evolutionarily, but unrelated to previously characterized phosphatidylinositol kinases, and thus represent the founding members of a new family. The novel phosphatidylinositol 4-kinases, which are widely expressed in cells, only phosphorylate phosphatidylinositol, are potently inhibited by adenosine, but are insensitive to wortmannin or phenylarsine oxide. Although they lack an obvious transmembrane domain, they are strongly attached to membranes by palmitoylation. Our data suggest that independent pathways for phosphatidylinositol 4-phosphate synthesis emerged during evolution, possibly to allow tight temporal and spatial control over the production of this key signaling molecule.