PMID- 9346907
OWN - NLM
STAT- MEDLINE
DCOM- 19971209
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 272
IP  - 44
DP  - 1997 Oct 31
TI  - STT4 is an essential phosphatidylinositol 4-kinase that is a target of wortmannin 
      in Saccharomyces cerevisiae.
PG  - 27671-7
AB  - Wortmannin is a natural product that inhibits signal transduction. One target of 
      wortmannin in mammalian cells is the 110-kDa catalytic subunit of 
      phosphatidylinositol 3-kinase (PI 3-kinase). We show that wortmannin is toxic to 
      the yeast Saccharomyces cerevisiae and present genetic and biochemical evidence 
      that a phosphatidylinositol 4-kinase (PI 4-kinase), STT4, is a target of 
      wortmannin in yeast. In a strain background in which stt4 mutants are rescued by 
      osmotic support with sorbitol, the toxic effects of wortmannin are similarly 
      prevented by sorbitol. In contrast, in a different strain background, STT4 is 
      essential under all conditions and wortmannin toxicity is not mitigated by 
      sorbitol. Overexpression of STT4 confers wortmannin resistance, but 
      overexpression of PIK1, a related PI 4-kinase, does not. In vitro, the PI 
      4-kinase activity of STT4, but not of PIK1, was potently inhibited by wortmannin. 
      Overexpression of the phosphatidylinositol 4-phosphate 5-kinase homolog MSS4 
      conferred wortmannin resistance, as did deletion of phospholipase C-1. These 
      observations support a model for a phosphatidylinositol metabolic cascade 
      involving STT4, MSS4, and phospholipase C-1 and provide evidence that an 
      essential product of this pathway is the lipid phosphatidylinositol 
      4,5-bisphosphate.
FAU - Cutler, N S
AU  - Cutler NS
AD  - Department of Genetics, Duke University Medical Center, Durham, North Carolina 
      27710, USA.
FAU - Heitman, J
AU  - Heitman J
FAU - Cardenas, M E
AU  - Cardenas ME
LA  - eng
GR  - P01-HL50985-01/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Androstadienes)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - EC 2.7.1.67 (1-Phosphatidylinositol 4-Kinase)
RN  - EC 2.7.1.67 (PIK1 protein, S cerevisiae)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - 1-Phosphatidylinositol 4-Kinase/*antagonists & inhibitors/genetics
MH  - Androstadienes/*pharmacology
MH  - Cell Membrane/enzymology/metabolism
MH  - Enzyme Inhibitors/*pharmacology
MH  - Mutation
MH  - Saccharomyces cerevisiae/drug effects/enzymology
MH  - *Saccharomyces cerevisiae Proteins
MH  - Type C Phospholipases/genetics
MH  - Wortmannin
EDAT- 1997/11/05 00:00
MHDA- 1997/11/05 00:01
CRDT- 1997/11/05 00:00
PHST- 1997/11/05 00:00 [pubmed]
PHST- 1997/11/05 00:01 [medline]
PHST- 1997/11/05 00:00 [entrez]
AID - S0021-9258(18)80312-X [pii]
AID - 10.1074/jbc.272.44.27671 [doi]
PST - ppublish
SO  - J Biol Chem. 1997 Oct 31;272(44):27671-7. doi: 10.1074/jbc.272.44.27671.