The stress-activated phosphatidylinositol 3-phosphate 5-kinase Fab1p is essential for vacuole function in S. cerevisiae

Curr Biol. 1998 Nov 5;8(22):1219-22. doi: 10.1016/s0960-9822(07)00513-1.


Polyphosphoinositides have many roles in cell signalling and vesicle trafficking [1-3]. Phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), a recently discovered PIP2 isomer, is ubiquitous in eukaryotic cells and rapidly accumulates in hyperosmotically stressed yeast. PI(3,5)P2 is synthesised from PI(3)P in both yeast and mammalian cells [4,5]. A search of the Saccharomyces cerevisiae genome database identified FAB1, a gene encoding a PIP kinase homologue and potential PI(3)P 5-kinase. Fab1p shows PI(3)P 5-kinase activity both in vivo and in vitro. A yeast strain in which FAB1 had been deleted was unable to synthesise PI(3,5)P2, either in the presence or absence of osmotic shock. A loss of PI(3,5)P2 was observed also in a temperature-sensitive FAB1 strain at the non-permissive temperature. A recombinant glutathione-S-transferase (GST)-Fab1p fusion protein was shown to have selective PI(3)P 5-kinase activity in vitro. Thus, we have demonstrated that Fab1p is a PI(3)P-specific 5-kinase and represents a third class of PIP kinase activity, which we have termed type III. Deletion of the FAB1 gene produces a loss of vacuolar morphology [6]; it is therefore concluded that PI(3,5)P2, the lipid product of Fab1p, is required for normal vacuolar function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Mutagenesis
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphatidylinositol Phosphates / metabolism*
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Phosphotransferases (Alcohol Group Acceptor) / physiology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / physiology
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins*
  • Substrate Specificity
  • Vacuoles


  • Phosphatidylinositol Phosphates
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • phosphatidylinositol 3,5-diphosphate
  • phosphatidylinositol 3-phosphate
  • phosphatidylinositol 4-phosphate
  • phosphatidylinositol 5-phosphate
  • FAB1 protein, S cerevisiae
  • Phosphotransferases (Alcohol Group Acceptor)
  • 1-phosphatidylinositol-4-phosphate 5-kinase