PMID- 10567352
OWN - NLM
STAT- MEDLINE
DCOM- 19991229
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 48
DP  - 1999 Nov 26
TI  - Complementation analysis in PtdInsP kinase-deficient yeast mutants demonstrates
      that Schizosaccharomyces pombe and murine Fab1p homologues are
      phosphatidylinositol 3-phosphate 5-kinases.
PG  - 33905-12
AB  - Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P(2)) is widespread in
      eukaryotic cells. In Saccharomyces cerevisiae, PtdIns(3,5)P(2) synthesis is
      catalyzed by the PtdIns3P 5-kinase Fab1p, and loss of this activity results in
      vacuolar morphological defects, indicating that PtdIns(3,5)P(2) is essential for 
      vacuole homeostasis. We have therefore suggested that all Fab1p homologues may be
      PtdIns3P 5-kinases involved in membrane trafficking. It is unclear which
      phosphatidylinositol phosphate kinases (PIPkins) are responsible for
      PtdIns(3,5)P(2) synthesis in higher eukaryotes. To clarify how PtdIns(3,5)P(2) is
      synthesized in mammalian and other cells, we determined whether yeast and
      mammalian Fab1p homologues or mammalian Type I PIPkins (PtdIns4P 5-kinases) make 
      PtdIns(3,5)P(2) in vivo. The recently cloned murine (p235) and
      Schizosaccharomyces pombe FAB1 homologues both restored basal PtdIns(3,5)P(2)
      synthesis in Deltafab1 cells and made PtdIns(3,5)P(2) in vitro. Only p235
      corrected the growth and vacuolar defects of fab1 S. cerevisiae. A mammalian Type
      I PIPkin supported no PtdIns(3,5)P(2) synthesis. Thus, FAB1 and its homologues
      constitute a distinct class of Type III PIPkins dedicated to PtdIns(3,5)P(2)
      synthesis. The differential abilities of p235 and of SpFab1p to complement the
      phenotypic defects of Deltafab1 cells suggests that interaction(s) with other
      protein factors may be important for spatial and/or temporal regulation of
      PtdIns(3,5)P(2) synthesis. These results also suggest that p235 may regulate a
      step in membrane trafficking in mammalian cells that is analogous to its function
      in yeast.
FAU - McEwen, R K
AU  - McEwen RK
AD  - School of Biochemistry, Centre for Clinical Research in Immunology and
      Signalling, University of Birmingham, Birmingham B15 2TT, United Kingdom.
      R.K.McEwen@bham.ac.uk
FAU - Dove, S K
AU  - Dove SK
FAU - Cooke, F T
AU  - Cooke FT
FAU - Painter, G F
AU  - Painter GF
FAU - Holmes, A B
AU  - Holmes AB
FAU - Shisheva, A
AU  - Shisheva A
FAU - Ohya, Y
AU  - Ohya Y
FAU - Parker, P J
AU  - Parker PJ
FAU - Michell, R H
AU  - Michell RH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Phosphatidylinositol 4,5-Diphosphate)
RN  - 0 (Phosphatidylinositol Phosphates)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (phosphatidylinositol 3,5-diphosphate)
RN  - EC 2.7.1.- (FAB1 protein, S cerevisiae)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.68 (1-phosphatidylinositol-4-phosphate 5-kinase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Chromatography, High Pressure Liquid
MH  - *Genetic Complementation Test
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Phenotype
MH  - Phosphatidylinositol 4,5-Diphosphate/biosynthesis
MH  - Phosphatidylinositol Phosphates/biosynthesis
MH  - Phosphotransferases (Alcohol Group Acceptor)/*deficiency/genetics/*metabolism
MH  - Saccharomyces cerevisiae/*enzymology/genetics
MH  - *Saccharomyces cerevisiae Proteins
MH  - Schizosaccharomyces/*enzymology/genetics
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
AID - 10.1074/jbc.274.48.33905 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Nov 26;274(48):33905-12. doi: 10.1074/jbc.274.48.33905.