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Gene Review

STT4  -  1-phosphatidylinositol 4-kinase STT4

Saccharomyces cerevisiae S288c

Synonyms: L2142.4, PI4-kinase, Phosphatidylinositol 4-kinase STT4, PtdIns-4-kinase, YLR305C
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Disease relevance of STT4

  • In contrast, in a different strain background, STT4 is essential under all conditions and wortmannin toxicity is not mitigated by sorbitol [1].
  • The heterologous expression of the S. cerevisiae LSB6 gene in Escherichia coli resulted in the expression of a protein that possessed PI 4-kinase activity [2].

High impact information on STT4

  • Expression of PIK1 from a multicopy plasmid elevated PtdIns 4-kinase activity and enhanced the response to mating pheromone [3].
  • Cells carrying PIK1 on a multicopy vector overexpress PI 4-kinase activity exclusively in a nuclear fraction, suggesting that PIK1 is part of a nuclear phosphoinositide cycle [4].
  • Interestingly, inactivation of Pik1p, a wortmannin-insensitive, functionally distinct PI4K, implicated in the regulation of Golgi functions and secretion, also results in severe translation initiation defects with a marked increase of the phosphorylation of the translation initiation factor eIF2alpha [5].
  • A primary target of wortmannin in yeast is the plasma membrane-associated PI 4-kinase (PI4K) Stt4p, which is required for actin cytoskeleton organization [5].
  • Overexpression of Pik1p, a PtdIns 4-kinase, suppressed the sec14-1 meiosis and spore formation defects; conversely, pik1-ts diploids failed to undergo meiosis and spore formation [6].

Biological context of STT4

  • The nucleotide sequence of STT4 predicts a hydrophilic protein composed of 1,900 amino acid residues, with 26% sequence identity to the yeast VPS34 gene product and 27% to the catalytic subunit of mammalian phosphatidylinositol (PI) 3-kinase, respectively [7].
  • The deduced amino acid sequence shared the identity of 52.3 and 34.4% in the presumed catalytic domain with two yeast PI 4-kinases, STT4 and PIK1, respectively, and showed 31.7% identity to p110alpha subunit of rat PI 3-kinase in the same domain [8].
  • The gene STT4, is essential for viability and encodes a phosphatidylinositol 4-kinase that plays an important role in the phosphatidylinositol-mediated signal transduction pathway required for cell wall integrity [9].
  • In addition, multicopy plasmids containing the LSB6 gene directed the overexpression of PI 4-kinase activity in cell extracts of wild-type cells, in an lsb6Delta mutant, in a pik1(ts) stt4(ts) double mutant, and in an pik1(ts) stt4(ts) lsb6Delta triple mutant [2].
  • In addition, a 3' half coding region of the present cDNA was 89.6% identical to and its deduced amino acid sequence was 98.2% identical to the sequence for P14Kalpha, a recently reported human PI 4-kinase of type II, suggesting that P14Kalpha is an alternative form of the present PI 4-kinase molecule [8].

Anatomical context of STT4


Associations of STT4 with chemical compounds

  • Both gene products phosphorylate PtdIns at the D-4 position of the inositol ring to generate PtdIns(4)P, which plays an essential role in yeast viability because deletion of either STT4 or PIK1 is lethal [13].
  • 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 [1].
  • The enzymological properties (pH optimum, dependence on magnesium or manganese as a cofactor, the dependence of activity on Triton X-100, the dependence on the PI surface concentration, and temperature sensitivity) of the LSB6-encoded enzyme were very similar to the membrane-associated 55-kDa PI 4-kinase previously purified from S. cerevisiae [2].
  • This PI 4-kinase activity was markedly enhanced in the presence of Triton X-100 but relatively insensitive to inhibition by adenosine [8].
  • Two distinct structural families of phosphoinositide (PI) kinases have so far been identified and named after their prototypic members, the PI 3-kinase and phosphatidylinositol (PtdIns) phosphate kinase families, both of which have been found to contain structural homologues possessing PI 4-kinase activity [14].

Other interactions of STT4

  • The yeast Saccharomyces cerevisiae contains two known phosphoinositide 4-kinases (PI 4-kinases), which are encoded by PIK1 and STT4; both are essential [15].
  • This effect is specific because overexpression of the other PtdIns 4-kinase gene (STT4) or a PtdIns 3-kinase gene (VPS34) did not rescue sec14-3 cells [16].
  • A novel gene, STT4, encodes a phosphatidylinositol 4-kinase in the PKC1 protein kinase pathway of Saccharomyces cerevisiae [7].
  • The physiological relevance of CDP-diacylglycerol inhibition of 45-kDa PI 4-kinase activity was examined using plasma membranes from inositol auxotrophic (ino1) cells [17].

Analytical, diagnostic and therapeutic context of STT4

  • By in situ hybridization analysis, the expression of mRNA for this PI 4-kinase was evident throughout the gray matter of entire brain with higher expression intensity in fetal brain [8].
  • In cell cultures, overexpression of Type I PIP5-kinase specifically increases PIP(2), whereas overexpression of Type II PI4-kinase can increase both PIP and PIP(2) [18].
  • The PIK1 gene encoding a PtdIns 4-kinase from the yeast Saccharomyces cerevisiae was isolated by polymerase chain reaction (PCR) with oligonucleotides based on the sequence of peptides derived from the purified enzyme [3].


  1. STT4 is an essential phosphatidylinositol 4-kinase that is a target of wortmannin in Saccharomyces cerevisiae. Cutler, N.S., Heitman, J., Cardenas, M.E. J. Biol. Chem. (1997) [Pubmed]
  2. The Saccharomyces cerevisiae LSB6 gene encodes phosphatidylinositol 4-kinase activity. Han, G.S., Audhya, A., Markley, D.J., Emr, S.D., Carman, G.M. J. Biol. Chem. (2002) [Pubmed]
  3. Phosphatidylinositol 4-kinase: gene structure and requirement for yeast cell viability. Flanagan, C.A., Schnieders, E.A., Emerick, A.W., Kunisawa, R., Admon, A., Thorner, J. Science (1993) [Pubmed]
  4. PIK1, an essential phosphatidylinositol 4-kinase associated with the yeast nucleus. Garcia-Bustos, J.F., Marini, F., Stevenson, I., Frei, C., Hall, M.N. EMBO J. (1994) [Pubmed]
  5. Phosphatidylinositol 4-Phosphate Is Required for Translation Initiation in Saccharomyces cerevisiae. Cameroni, E., De Virgilio, C., Deloche, O. J. Biol. Chem. (2006) [Pubmed]
  6. Roles of phosphoinositides and of Spo14p (phospholipase D)-generated phosphatidic acid during yeast sporulation. Rudge, S.A., Sciorra, V.A., Iwamoto, M., Zhou, C., Strahl, T., Morris, A.J., Thorner, J., Engebrecht, J. Mol. Biol. Cell (2004) [Pubmed]
  7. A novel gene, STT4, encodes a phosphatidylinositol 4-kinase in the PKC1 protein kinase pathway of Saccharomyces cerevisiae. Yoshida, S., Ohya, Y., Goebl, M., Nakano, A., Anraku, Y. J. Biol. Chem. (1994) [Pubmed]
  8. Cloning, expression, and localization of 230-kDa phosphatidylinositol 4-kinase. Nakagawa, T., Goto, K., Kondo, H. J. Biol. Chem. (1996) [Pubmed]
  9. Cloning, characterization and identification of the gene encoding phosphatidylinositol 4-kinase. Pramanik, A., Garcia, E., Ospina, R., Powell, M., Martinez, M., Alejo, W., McKoy, J., Moore, C.W. Cell. Mol. Biol. (Noisy-le-grand) (1997) [Pubmed]
  10. Regulation of intracellular phosphatidylinositol-4-phosphate by the Sac1 lipid phosphatase. Tahirovic, S., Schorr, M., Mayinger, P. Traffic (2005) [Pubmed]
  11. Stt4 PI 4-kinase localizes to the plasma membrane and functions in the Pkc1-mediated MAP kinase cascade. Audhya, A., Emr, S.D. Dev. Cell (2002) [Pubmed]
  12. Subcellular locations of phosphatidylinositol 4-kinase isoforms. Wong, K., Meyers ddR, n.u.l.l., Cantley, L.C. J. Biol. Chem. (1997) [Pubmed]
  13. Distinct roles for the yeast phosphatidylinositol 4-kinases, Stt4p and Pik1p, in secretion, cell growth, and organelle membrane dynamics. Audhya, A., Foti, M., Emr, S.D. Mol. Biol. Cell (2000) [Pubmed]
  14. Cloning of a human type II phosphatidylinositol 4-kinase reveals a novel lipid kinase family. Minogue, S., Anderson, J.S., Waugh, M.G., dos Santos, M., Corless, S., Cramer, R., Hsuan, J.J. J. Biol. Chem. (2001) [Pubmed]
  15. Saccharomyces cerevisiae contains a Type II phosphoinositide 4-kinase. Shelton, S.N., Barylko, B., Binns, D.D., Horazdovsky, B.F., Albanesi, J.P., Goodman, J.M. Biochem. J. (2003) [Pubmed]
  16. Direct involvement of phosphatidylinositol 4-phosphate in secretion in the yeast Saccharomyces cerevisiae. Hama, H., Schnieders, E.A., Thorner, J., Takemoto, J.Y., DeWald, D.B. J. Biol. Chem. (1999) [Pubmed]
  17. Regulation of phosphatidylinositol 4-kinase from the yeast Saccharomyces cerevisiae by CDP-diacylglycerol. Nickels, J.T., Buxeda, R.J., Carman, G.M. J. Biol. Chem. (1994) [Pubmed]
  18. Nonradioactive analysis of phosphatidylinositides and other anionic phospholipids by anion-exchange high-performance liquid chromatography with suppressed conductivity detection. Nasuhoglu, C., Feng, S., Mao, J., Yamamoto, M., Yin, H.L., Earnest, S., Barylko, B., Albanesi, J.P., Hilgemann, D.W. Anal. Biochem. (2002) [Pubmed]
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