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Gene Review

PIK1  -  1-phosphatidylinositol 4-kinase

Saccharomyces cerevisiae S288c

Synonyms: N0795, PI4-kinase, PIK120, PIK41, Phosphatidylinositol 4-kinase PIK1, ...
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High impact information on PIK1


Biological context of PIK1

  • Correspondingly, we found that PtdIns(4)P levels were decreased significantly in sec14-3 mutants shifted to 37 degrees C and that sec14-3 cells could grow at an otherwise nonpermissive temperature (34 degrees C) when carrying a plasmid overexpressing PIK1, encoding one of two essential PtdIns 4-kinases [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].
  • Distinct roles for the yeast phosphatidylinositol 4-kinases, Stt4p and Pik1p, in secretion, cell growth, and organelle membrane dynamics [7].
  • In contrast, Pik1p is essential for normal secretion, Golgi and vacuole membrane dynamics, and endocytosis [7].
  • Although Pik1p and Stt4p are closely related members of the Type III class of PI 4-kinases, Lsb6p belongs to the distinct Type II class, based on its amino acid sequence, its sensitivity to inhibition by adenosine and its insensitivity to wortmannin [8].

Anatomical context of PIK1

  • Based on these results, we propose that Stt4p and Pik1p act as the major, if not the only, PtdIns 4-kinases in yeast and produce distinct pools of PtdIns(4)P and PtdIns(4,5)P(2) that act on different intracellular membranes to recruit or activate as yet uncharacterized effector proteins [7].
  • Pik1p is important for exocytic transport from the Golgi, whereas Stt4p plays a role in cell-wall integrity and cytoskeletal rearrangements [8].
  • Studies with mutants of phosphatidylinositol 4-kinase, PIK1, suggested that the interaction with membranes is facilitated by phosphoinositides [9].

Associations of PIK1 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 [7].
  • 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].
  • In Saccharomyces cerevisiae, the phosphatidylinositol 4-kinase, Pik1p generates a distinct pool of PtdIns(4)P that is required for normal Golgi structure and secretory function [10].
  • In contrast, phosphatidylinositol 4-phosphate generated by Pik1p localized in intracellular compartments [11].

Other interactions of PIK1

  • In vitro, the PI 4-kinase activity of STT4, but not of PIK1, was potently inhibited by wortmannin [12].
  • These findings indicate that, first, PtdIns(4)P limitation is a major contributing factor to the secretory defect in sec14 cells; second, Sec14p function is coupled to the action of Pik1p, and; third, PtdIns(4)P has an important role in the Golgi-to-plasma membrane stage of secretion [5].
  • Thus, rather than a role for PtdOH in stimulating PtdIns(4,5)P2 formation, our findings indicate that during sporulation, Spo14p-mediated PtdOH production functions downstream of Sec14p-, Pik1p-, and Mss4p-dependent PtdIns(4,5)P2 synthesis [6].
  • N-myristoylated Frq1 may also assist in Pik1 localization [2].
  • This targeting is independent of Pik1p but dependent on the Golgi GTPase Arf1p [13].

Analytical, diagnostic and therapeutic context of PIK1


  1. 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]
  2. Yeast homologue of neuronal frequenin is a regulator of phosphatidylinositol-4-OH kinase. Hendricks, K.B., Wang, B.Q., Schnieders, E.A., Thorner, J. Nat. Cell Biol. (1999) [Pubmed]
  3. Yeast phosphatidylinositol 4-kinase, Pik1, has essential roles at the Golgi and in the nucleus. Strahl, T., Hama, H., DeWald, D.B., Thorner, J. J. Cell Biol. (2005) [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. 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]
  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. 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]
  8. 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]
  9. Bsp1p/Ypr171p is an adapter that directly links some synaptojanin family members to the cortical actin cytoskeleton in yeast. Wicky, S., Frischmuth, S., Singer-Krüger, B. FEBS Lett. (2003) [Pubmed]
  10. Synthetic genetic array analysis of the PtdIns 4-kinase Pik1p identifies components in a Golgi-specific Ypt31/rab-GTPase signaling pathway. Sciorra, V.A., Audhya, A., Parsons, A.B., Segev, N., Boone, C., Emr, S.D. Mol. Biol. Cell (2005) [Pubmed]
  11. The yeast synaptojanin-like proteins control the cellular distribution of phosphatidylinositol (4,5)-bisphosphate. Stefan, C.J., Audhya, A., Emr, S.D. Mol. Biol. Cell (2002) [Pubmed]
  12. 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]
  13. Targeting of Golgi-specific pleckstrin homology domains involves both PtdIns 4-kinase-dependent and -independent components. Levine, T.P., Munro, S. Curr. Biol. (2002) [Pubmed]
  14. Conservation of regulatory function in calcium-binding proteins: human frequenin (neuronal calcium sensor-1) associates productively with yeast phosphatidylinositol 4-kinase isoform, Pik1. Strahl, T., Grafelmann, B., Dannenberg, J., Thorner, J., Pongs, O. J. Biol. Chem. (2003) [Pubmed]
  15. Molecular interactions of yeast frequenin (Frq1) with the phosphatidylinositol 4-kinase isoform, Pik1. Huttner, I.G., Strahl, T., Osawa, M., King, D.S., Ames, J.B., Thorner, J. J. Biol. Chem. (2003) [Pubmed]
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