Osmotic stress activates phosphatidylinositol-3,5-bisphosphate synthesis

Stephen K. Dove*, Frank T. Cooke, Michael R. Douglas, Lee G. Sayers, Peter J. Parker, Robert H. Michell

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

378 Citations (Scopus)


Inositol phospholipids play multiple roles in cell signaling systems. Two widespread eukaryotic phosphoinositide-based signal transduction mechanisms, phosphoinositidase C-catalysed phosphatidylinositol-4,5- bisphosphate (PtdIns(4,5)P2) hydrolysis and 3-OH kinase-catalysed PtdIns(4,5)P2 phosphorylation, make the second messengers inositol 1,4,5- trisphosphate (Ins(1,4,5)P3) sn-1,2-diacylglycerol and PtdIns(3,4,5)P3 (refs 1-7). In addition, PtdIns(4,5)P2 and PtdIns3P have been implicated in exocytosis and membrane trafficking. We now show that when the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe are hyperosmotically stressed, they rapidly synthesize phosphatidy-linositol-3,5-bisphosphate (PtdIns(3,5)P2) by a process that involves activation of a PtdIns3P 5-OH kinase. This PtdIns(3,5)P2 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)P2 synthesis and indicating that PtdIns(3,5)P2 may have a role in sorting vesicular proteins. PtdIns(3,5)P2 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)P2, 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.

Original languageEnglish
Pages (from-to)187-192
Number of pages6
Issue number6656
Publication statusPublished - 13 Nov 1997

ASJC Scopus subject areas

  • General Medicine
  • General


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