Osmotic stress activates phosphatidylinositol-3,5-bisphosphate synthesis
Osmotic stress activates phosphatidylinositol-3,5-bisphosphate synthesis
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DOI：
10.1038/36613
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发表时间：
1997-11-13
期刊：
影响因子：
64.8
通讯作者：
Michell, RH
中科院分区：
文献类型：
--
作者：
Dove, SK;Cooke, FT;Michell, RH
肌醇磷脂在细胞信号系统中发挥多种作用。两种广泛存在的基于真核磷酸肌醇的信号转导机制，即磷酸肌醇酶C催化的磷脂酰肌醇-4，5-二磷酸（PtdIns（4，5）P-2）水解和3-OH激酶催化的PtdIns（4，5）P-2磷酸化，产生第二信使肌醇1，4，5-三磷酸（Ins（1，4，5）P-3）sn-1，2-二酰基甘油和PtdIns（3，4，5）P-3（参考文献1-7）。此外，PtdIns（4，5）P-2和PtdIns 3 P与胞吐作用和膜运输有关（8）。我们现在表明，当酵母酿酒酵母和裂殖酵母高血压强调，他们迅速合成磷脂酰肌醇-3，5-二磷酸（PtdIns（3，5）P-2）的过程中，涉及激活PtdIns 3 P 5-OH激酶。这种PtdIns（3，5）P-2积累仅发生在具有活性vps 34编码的PtdIns 3-OH激酶的酵母中，表明后一种激酶产生PtdIns（3，5）P-2合成所需的PtdIns 3 P，并表明PtdIns（3，5）P-2可能在分选囊泡蛋白中起作用。PtdIns（3，5）P-2也存在于哺乳动物和植物细胞中：在猴Cos-7细胞中，其标记与外部渗透压呈负相关。PtdIns 3 P 5-OH激酶催化合成PtdIns（3，5）P-2（一种可能是新型磷酸肌醇“第二信使”的分子）的刺激，因此似乎是一种广泛存在且以前未表征的调节途径的核心。
Inositol phospholipids play multiple roles in cell signalling systems. Two widespread eukaryotic phosphoinositide-based signal transduction mechanisms, phosphoinositidase C-catalysed phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P-2) hydrolysis and 3-OH kinase-catalysed PtdIns(4,5)P-2 phosphorylation, make the second messengers inositol 1,4,5-trisphosphate (Ins(1,4,5)P-3) sn-1,2-diacylglycerol and PtdIns(3,4,5)P-3 (refs 1-7). In addition, PtdIns(4,5)P-2 and PtdIns3P have been implicated in exocytosis and membrane trafficking(8). We now show that when the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe are hyperosmotically stressed, they rapidly synthesize phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P-2) by a process that involves activation of a PtdIns3P 5-OH kinase. This PtdIns(3,5)P-2 accumulation only occurs in yeasts that have an active vps34-encoded PtdIns 3-OH kinase, showing that this latter kinase makes the PtdIns3P needed for PtdIns(3,5)P-2 synthesis and indicating that PtdIns(3,5)P-2 may have a role in sorting vesicular proteins. PtdIns(3,5)P-2 is also present in mammalian and plant cells: in monkey Cos-7 cells, its labelling is inversely related to the external osmotic pressure. The stimulation of a PtdIns3P 5-OH kinase-catalysed synthesis of PtdIns(3,5)P-2, a molecule that might be a new type of phosphoinositide 'second messenger', thus appears to be central to a widespread and previously uncharacterized regulatory pathway.