1 phosphatidylinositol 4 kinase


Summary: An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.

Top Publications

  1. Garcia Bustos J, Marini F, Stevenson I, Frei C, Hall M. PIK1, an essential phosphatidylinositol 4-kinase associated with the yeast nucleus. EMBO J. 1994;13:2352-61 pubmed
    ..Conditional mutants have a cytokinesis defect as indicated by a uniform terminal phenotype of cells with large buds and fully divided nuclei. We suggest that PIK1 controls cytokinesis through the actin cytoskeleton. ..
  2. Guo J, Wenk M, Pellegrini L, Onofri F, Benfenati F, De Camilli P. Phosphatidylinositol 4-kinase type IIalpha is responsible for the phosphatidylinositol 4-kinase activity associated with synaptic vesicles. Proc Natl Acad Sci U S A. 2003;100:3995-4000 pubmed
    ..Our results provide new evidence for the occurrence of a cycle of phosphoinositide synthesis and hydrolysis nested within the exo-endocytic cycle of synaptic vesicles and point to PI4KIIalpha as a critical player in this cycle. ..
  3. Audhya A, Foti M, Emr S. Distinct roles for the yeast phosphatidylinositol 4-kinases, Stt4p and Pik1p, in secretion, cell growth, and organelle membrane dynamics. Mol Biol Cell. 2000;11:2673-89 pubmed
  4. Heck J, Mellman D, Ling K, Sun Y, Wagoner M, Schill N, et al. A conspicuous connection: structure defines function for the phosphatidylinositol-phosphate kinase family. Crit Rev Biochem Mol Biol. 2007;42:15-39 pubmed
  5. Rodgers M, Albanesi J, Phillips M. Phosphatidylinositol 4-kinase III-beta is required for Golgi maintenance and cytokinesis in Trypanosoma brucei. Eukaryot Cell. 2007;6:1108-18 pubmed
    ..In summary, TbPI4KIII-beta is an essential protein in procyclic T. brucei, required for maintenance of Golgi structure, protein trafficking, normal cellular shape, and cytokinesis. ..
  6. Yoshida S, Ohya Y, Goebl M, Nakano A, Anraku Y. A novel gene, STT4, encodes a phosphatidylinositol 4-kinase in the PKC1 protein kinase pathway of Saccharomyces cerevisiae. J Biol Chem. 1994;269:1166-72 pubmed
    ..We conclude that STT4 encodes a yeast PI4-kinase that functions in the PKC1 protein kinase pathway. ..
  7. Balla T, Downing G, Jaffe H, Kim S, Zolyomi A, Catt K. Isolation and molecular cloning of wortmannin-sensitive bovine type III phosphatidylinositol 4-kinases. J Biol Chem. 1997;272:18358-66 pubmed
    ..5-kb transcript. The molecular cloning of these novel WT-sensitive type III PI 4-kinases will allow detailed analysis of their signaling and other regulatory functions in mammalian cells. ..
  8. Muhua L, Adames N, Murphy M, Shields C, Cooper J. A cytokinesis checkpoint requiring the yeast homologue of an APC-binding protein. Nature. 1998;393:487-91 pubmed
    ..Another mutation affects Stt4, a phosphatidylinositol-4-OH kinase. Cold temperature is an environmental stimulus that causes misalignment of the mitotic spindle in yeast and appears to activate this checkpoint mechanism. ..
  9. Waugh M, Minogue S, Anderson J, Balinger A, Blumenkrantz D, Calnan D, et al. Localization of a highly active pool of type II phosphatidylinositol 4-kinase in a p97/valosin-containing-protein-rich fraction of the endoplasmic reticulum. Biochem J. 2003;373:57-63 pubmed
    ..Co-localization of VCP and PI4K activity was confirmed by co-immunoprecipitation. These results suggest the previously unsuspected existence of an ER-related domain in which the bulk of the cellular PI4P synthesis and VCP are localized. ..

More Information


  1. Nishikawa K, Toker A, Wong K, Marignani P, Johannes F, Cantley L. Association of protein kinase Cmu with type II phosphatidylinositol 4-kinase and type I phosphatidylinositol-4-phosphate 5-kinase. J Biol Chem. 1998;273:23126-33 pubmed
    ..These results suggest a novel model in which the non-catalytic region of PKCmu acts as a scaffold for assembly of enzymes involved in phosphoinositide synthesis at specific membrane locations. ..
  2. Hendricks K, Wang B, Schnieders E, Thorner J. Yeast homologue of neuronal frequenin is a regulator of phosphatidylinositol-4-OH kinase. Nat Cell Biol. 1999;1:234-41 pubmed
    ..Frq1 binds to a conserved sequence motif in Pik1 outside Pik1's catalytic domain and stimulates its activity in vitro. N-myristoylated Frq1 may also assist in Pik1 localization. ..
  3. Roy A, Levine T. Multiple pools of phosphatidylinositol 4-phosphate detected using the pleckstrin homology domain of Osh2p. J Biol Chem. 2004;279:44683-9 pubmed
    ..For example, in cells with excess PtdIns(4)P caused by inactivation of the phosphatase Sac1p, PH(Osh2) indicates that PtdIns(4)P accumulates on the plasma membrane, whereas other Golgi-targeted PH domains fail to detect this change. ..
  4. Foti M, Audhya A, Emr S. Sac1 lipid phosphatase and Stt4 phosphatidylinositol 4-kinase regulate a pool of phosphatidylinositol 4-phosphate that functions in the control of the actin cytoskeleton and vacuole morphology. Mol Biol Cell. 2001;12:2396-411 pubmed
    ..Regulation of this PtdIns(4)P pool appears to be crucial for the maintenance of vacuole morphology, regulation of lipid storage, Golgi function, and actin cytoskeleton organization. ..
  5. Xie Z, Fang M, Bankaitis V. Evidence for an intrinsic toxicity of phosphatidylcholine to Sec14p-dependent protein transport from the yeast Golgi complex. Mol Biol Cell. 2001;12:1117-29 pubmed
    ..Taken together, these data support the idea that PtdCho is intrinsically toxic to yeast Golgi secretory function. ..
  6. Minogue S, Anderson J, Waugh M, dos Santos M, Corless S, Cramer R, et al. Cloning of a human type II phosphatidylinositol 4-kinase reveals a novel lipid kinase family. J Biol Chem. 2001;276:16635-40 pubmed
    ..We have named the purified protein type IIalpha and a second human isoform, type IIbeta. The type IIalpha mRNA appears to be expressed ubiquitously in human tissues, and homologues appear to be expressed in all eukaryotes. ..
  7. Wong K, Meyers ddR -, Cantley L. Subcellular locations of phosphatidylinositol 4-kinase isoforms. J Biol Chem. 1997;272:13236-41 pubmed
    ..Neither of these isoforms accounts for the major type II PtdIns 4-kinase activity detected in the lysosomes and plasma membrane fraction. ..
  8. Barylko B, Gerber S, Binns D, Grichine N, Khvotchev M, Sudhof T, et al. A novel family of phosphatidylinositol 4-kinases conserved from yeast to humans. J Biol Chem. 2001;276:7705-8 pubmed
    ..Our data suggest that independent pathways for phosphatidylinositol 4-phosphate synthesis emerged during evolution, possibly to allow tight temporal and spatial control over the production of this key signaling molecule. ..
  9. Huttner I, Strahl T, Osawa M, King D, Ames J, Thorner J. Molecular interactions of yeast frequenin (Frq1) with the phosphatidylinositol 4-kinase isoform, Pik1. J Biol Chem. 2003;278:4862-74 pubmed
    ..This study defines the segment of Pik1 required for high affinity binding of Frq1. ..
  10. Han G, Audhya A, Markley D, Emr S, Carman G. The Saccharomyces cerevisiae LSB6 gene encodes phosphatidylinositol 4-kinase activity. J Biol Chem. 2002;277:47709-18 pubmed
    ..cerevisiae. ..
  11. Huijbregts R, Topalof L, Bankaitis V. Lipid metabolism and regulation of membrane trafficking. Traffic. 2000;1:195-202 pubmed
    ..The 1990s, and particularly its last half, has brought fundamental reappraisals of the interface of lipids and lipid metabolism in regulating intracellular membrane trafficking events. Some of the emerging themes are reviewed here. ..
  12. Strahl T, Hama H, DeWald D, Thorner J. Yeast phosphatidylinositol 4-kinase, Pik1, has essential roles at the Golgi and in the nucleus. J Cell Biol. 2005;171:967-79 pubmed
    ..Catalytically inactive derivatives of these compartment-restricted Pik1 constructs indicated that PtdIns4P must be generated both in the nucleus and at the Golgi for normal cell function. ..
  13. Hinchliffe K, Irvine R. Regulation of type II PIP kinase by PKD phosphorylation. Cell Signal. 2006;18:1906-13 pubmed
    ..We conclude that the type II PIP kinases are physiological targets for PKD phosphorylation, and that this modification is likely to regulate inositol lipid turnover by inhibition of these lipid kinases. ..
  14. Toth B, Balla A, Ma H, Knight Z, Shokat K, Balla T. Phosphatidylinositol 4-kinase IIIbeta regulates the transport of ceramide between the endoplasmic reticulum and Golgi. J Biol Chem. 2006;281:36369-77 pubmed
    ..Therefore, PI 4-kinase beta is a key enzyme in the control of spingomyelin synthesis by controlling the flow of ceramide from the ER to the Golgi compartment. ..
  15. Hama H, Schnieders E, Thorner J, Takemoto J, DeWald D. Direct involvement of phosphatidylinositol 4-phosphate in secretion in the yeast Saccharomyces cerevisiae. J Biol Chem. 1999;274:34294-300 pubmed
  16. Anderson R, Boronenkov I, Doughman S, Kunz J, Loijens J. Phosphatidylinositol phosphate kinases, a multifaceted family of signaling enzymes. J Biol Chem. 1999;274:9907-10 pubmed
  17. Xue H, Pical C, Brearley C, Elge S, Müller Röber B. A plant 126-kDa phosphatidylinositol 4-kinase with a novel repeat structure. Cloning and functional expression in baculovirus-infected insect cells. J Biol Chem. 1999;274:5738-45 pubmed
    ..AtPI4Kbeta transcript levels were similar in all tissues analyzed. Light or treatment with hormones or salts did not change AtPI4Kbeta transcript levels to a great extent, indicating constitutive expression of the AtPI4Kbeta gene. ..
  18. Strahl T, Thorner J. Synthesis and function of membrane phosphoinositides in budding yeast, Saccharomyces cerevisiae. Biochim Biophys Acta. 2007;1771:353-404 pubmed
  19. Chang F, Han G, Carman G, Blumer K. A WASp-binding type II phosphatidylinositol 4-kinase required for actin polymerization-driven endosome motility. J Cell Biol. 2005;171:133-42 pubmed
    ..Lsb6 therefore is a novel regulator of Las17 that mediates endosome motility independent of phosphatidylinositol 4-phosphate synthesis. Mammalian type II phosphatidylinositol 4-kinases may regulate WASp proteins and endosome motility. ..
  20. Hausser A, Storz P, Martens S, Link G, Toker A, Pfizenmaier K. Protein kinase D regulates vesicular transport by phosphorylating and activating phosphatidylinositol-4 kinase IIIbeta at the Golgi complex. Nat Cell Biol. 2005;7:880-6 pubmed
    ..The identification of PI4KIIIbeta as one of the PKD substrates should help to reveal the molecular events that enable transport-carrier formation. ..
  21. Balla A, Tuymetova G, Tsiomenko A, Varnai P, Balla T. A plasma membrane pool of phosphatidylinositol 4-phosphate is generated by phosphatidylinositol 4-kinase type-III alpha: studies with the PH domains of the oxysterol binding protein and FAPP1. Mol Biol Cell. 2005;16:1282-95 pubmed
    ..Our data suggest that these PH domains detect PI(4)P formation in extra-Golgi compartments under dynamic conditions and that various PI4Ks regulate PI(4)P synthesis in distinct cellular compartments. ..
  22. Sciorra V, Audhya A, Parsons A, Segev N, Boone C, Emr S. Synthetic genetic array analysis of the PtdIns 4-kinase Pik1p identifies components in a Golgi-specific Ypt31/rab-GTPase signaling pathway. Mol Biol Cell. 2005;16:776-93 pubmed
    ..We propose that multiple stage-specific signals, which may include Pik1p/PtdIns(4)P, TRAPPII and Gyp2p, impinge upon Ypt31 signaling to regulate Golgi secretory function. ..
  23. Carloni V, Mazzocca A, Ravichandran K. Tetraspanin CD81 is linked to ERK/MAPKinase signaling by Shc in liver tumor cells. Oncogene. 2004;23:1566-74 pubmed
    ..These findings define a novel mechanism of ERK/MAPKinase activation and tumor cell proliferation. ..
  24. Irvine R. Nuclear lipid signalling. Nat Rev Mol Cell Biol. 2003;4:349-60 pubmed
    ..However, exactly as has been discovered in the cytoplasm, this is just part of a complex picture that involves many other lipids and functions. ..
  25. Flanagan C, Schnieders E, Emerick A, Kunisawa R, Admon A, Thorner J. Phosphatidylinositol 4-kinase: gene structure and requirement for yeast cell viability. Science. 1993;262:1444-8 pubmed
    ..A pik1 null mutant was inviable, indicating that PtdIns4P and presumably PtdIns[4,5]P2 are indispensable phospholipids. ..
  26. Levine T, Munro S. Targeting of Golgi-specific pleckstrin homology domains involves both PtdIns 4-kinase-dependent and -independent components. Curr Biol. 2002;12:695-704 pubmed
  27. Balla A, Tuymetova G, Barshishat M, Geiszt M, Balla T. Characterization of type II phosphatidylinositol 4-kinase isoforms reveals association of the enzymes with endosomal vesicular compartments. J Biol Chem. 2002;277:20041-50 pubmed
    ..Our data indicate the existence of multiple forms of type II PI 4-kinase in mammalian cells and suggest that their functions are related to the endocytic pathway. ..
  28. Schorr M, Then A, Tahirovic S, Hug N, Mayinger P. The phosphoinositide phosphatase Sac1p controls trafficking of the yeast Chs3p chitin synthase. Curr Biol. 2001;11:1421-6 pubmed
  29. Vanhaesebroeck B, Leevers S, Ahmadi K, Timms J, Katso R, Driscoll P, et al. Synthesis and function of 3-phosphorylated inositol lipids. Annu Rev Biochem. 2001;70:535-602 pubmed
    ..This field is now moving toward a genetic dissection of 3-phosphoinositide action in a variety of model organisms. Such approaches will reveal the true role of the 3-phosphoinositides at the organismal level in health and disease. ..
  30. Barylko B, Wlodarski P, Binns D, Gerber S, Earnest S, Sudhof T, et al. Analysis of the catalytic domain of phosphatidylinositol 4-kinase type II. J Biol Chem. 2002;277:44366-75 pubmed
    ..Depletion of PI4KII from Drosophila cells resulted in a severe reduction of PtdIns 4-kinase activity, suggesting the in vivo importance of this enzyme. ..
  31. Heilmeyer L, Vereb G, Kakuk A, Szivak I. Mammalian phosphatidylinositol 4-kinases. IUBMB Life. 2003;55:59-65 pubmed
    ..PI4K55 is involved in the production of second messengers, diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (InsP3) at the plasma membrane, moreover, in the endocytotic pathway in the cytoplasm. ..
  32. Gozani O, Karuman P, Jones D, Ivanov D, Cha J, Lugovskoy A, et al. The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor. Cell. 2003;114:99-111 pubmed
    ..Together, our data identify the PHD finger as a phosphoinositide binding module and a nuclear PtdInsP receptor, and suggest that PHD-phosphoinositide interactions directly regulate nuclear responses to DNA damage. ..
  33. Strahl T, Grafelmann B, Dannenberg J, Thorner J, Pongs O. Conservation of regulatory function in calcium-binding proteins: human frequenin (neuronal calcium sensor-1) associates productively with yeast phosphatidylinositol 4-kinase isoform, Pik1. J Biol Chem. 2003;278:49589-99 pubmed
    ..We propose, therefore, that the function of NCS-1 in mammals may closely resemble that of Frq1 in S. cerevisiae and, hence, that frequenins in general may serve as regulators of certain isoforms of phosphatidylinositol 4-kinase. ..
  34. Meyers R, Cantley L. Cloning and characterization of a wortmannin-sensitive human phosphatidylinositol 4-kinase. J Biol Chem. 1997;272:4384-90 pubmed
    ..Catt, J. K., and Balla, T. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 5317-5321). ..
  35. Stevenson J, Perera I, Boss W. A phosphatidylinositol 4-kinase pleckstrin homology domain that binds phosphatidylinositol 4-monophosphate. J Biol Chem. 1998;273:22761-7 pubmed
    ..Consideration is given to the potential impact that this has on cytoskeletal organization and the PI signaling pathway in cells that have a high PI-4-P/PI-4,5-P2 ratio. ..
  36. Walch Solimena C, Novick P. The yeast phosphatidylinositol-4-OH kinase pik1 regulates secretion at the Golgi. Nat Cell Biol. 1999;1:523-5 pubmed
  37. Park J, Steinbach S, Desautels M, Hemmingsen S. Essential role for Schizosaccharomyces pombe pik1 in septation. PLoS ONE. 2009;4:e6179 pubmed publisher
    ..Thus, D709 is essential for kinase activity and septation. Pik1 kinase activity is required for septation. The Pik1 R838 residue is required for important protein-protein interactions, possibly with Cdc4. ..
  38. D Angelo G, Vicinanza M, Di Campli A, De Matteis M. The multiple roles of PtdIns(4)P -- not just the precursor of PtdIns(4,5)P2. J Cell Sci. 2008;121:1955-63 pubmed publisher
    ..The aim of this Commentary is to describe our present knowledge of PtdIns(4)P metabolism and the molecular machineries that are directly regulated by PtdIns(4)P within and outside of the Golgi complex. ..
  39. Balla A, Kim Y, Varnai P, Szentpetery Z, Knight Z, Shokat K, et al. Maintenance of hormone-sensitive phosphoinositide pools in the plasma membrane requires phosphatidylinositol 4-kinase IIIalpha. Mol Biol Cell. 2008;19:711-21 pubmed
  40. Tabuchi M, Audhya A, Parsons A, Boone C, Emr S. The phosphatidylinositol 4,5-biphosphate and TORC2 binding proteins Slm1 and Slm2 function in sphingolipid regulation. Mol Cell Biol. 2006;26:5861-75 pubmed
    ..Together, our data suggest that Slm1 and Slm2 define a molecular link between phosphoinositide and sphingolipid signaling and thereby regulate actin cytoskeleton organization. ..
  41. Brill J, Hime G, Scharer Schuksz M, Fuller M. A phospholipid kinase regulates actin organization and intercellular bridge formation during germline cytokinesis. Development. 2000;127:3855-64 pubmed
    ..Our results suggest a critical role for PI 4-kinases and phosphatidylinositol derivatives during the final stages of cytokinesis. ..
  42. Weixel K, Blumental Perry A, Watkins S, Aridor M, Weisz O. Distinct Golgi populations of phosphatidylinositol 4-phosphate regulated by phosphatidylinositol 4-kinases. J Biol Chem. 2005;280:10501-8 pubmed
    ..We discuss our results with respect to the kinetic effects of modulating PI4K activity on polarized biosynthetic traffic in MDCK cells. ..
  43. Stevenson Paulik J, Love J, Boss W. Differential regulation of two Arabidopsis type III phosphatidylinositol 4-kinase isoforms. A regulatory role for the pleckstrin homology domain. Plant Physiol. 2003;132:1053-64 pubmed
    ..These studies support the idea that the Arabidopsis type III PtdIns 4-kinases are responsible for distinct phosphoinositide pools. ..
  44. Preuss M, Schmitz A, Thole J, Bonner H, Otegui M, Nielsen E. A role for the RabA4b effector protein PI-4Kbeta1 in polarized expansion of root hair cells in Arabidopsis thaliana. J Cell Biol. 2006;172:991-8 pubmed
  45. Kapp Barnea Y, Ninio Many L, Hirschberg K, Fukuda M, Jeromin A, Sagi Eisenberg R. Neuronal calcium sensor-1 and phosphatidylinositol 4-kinase beta stimulate extracellular signal-regulated kinase 1/2 signaling by accelerating recycling through the endocytic recycling compartment. Mol Biol Cell. 2006;17:4130-41 pubmed
    ..Our results further identify the ERC as a crucial determinant in controlling ERK1/2 signaling. ..
  46. Desautels M, Den Haese J, Slupsky C, McIntosh L, Hemmingsen S. Cdc4p, a contractile ring protein essential for cytokinesis in Schizosaccharomyces pombe, interacts with a phosphatidylinositol 4-kinase. J Biol Chem. 2001;276:5932-42 pubmed
    ..We suggest that Cdc4p plays multiple roles in cytokinesis and that interaction with a PI 4-kinase may be important for contractile ring assembly and/or function. ..
  47. Zheng Q, Bobich J, Vidugiriene J, McFadden S, Thomas F, Roder J, et al. Neuronal calcium sensor-1 facilitates neuronal exocytosis through phosphatidylinositol 4-kinase. J Neurochem. 2005;92:442-51 pubmed
  48. Krauss M, Haucke V. Phosphoinositide-metabolizing enzymes at the interface between membrane traffic and cell signalling. EMBO Rep. 2007;8:241-6 pubmed
  49. Godi A, Pertile P, Meyers R, Marra P, Di Tullio G, Iurisci C, et al. ARF mediates recruitment of PtdIns-4-OH kinase-beta and stimulates synthesis of PtdIns(4,5)P2 on the Golgi complex. Nat Cell Biol. 1999;1:280-7 pubmed
    ..Phosphatidylinositol-4-OH kinase-beta is required for the structural integrity of the Golgi complex: transfection of a dominant-negative mutant of the kinase markedly alters the organization of the organelle. ..
  50. de Graaf P, Klapisz E, Schulz T, Cremers A, Verkleij A, van Bergen en Henegouwen P. Nuclear localization of phosphatidylinositol 4-kinase beta. J Cell Sci. 2002;115:1769-75 pubmed
    ..These data demonstrate that PtdIns 4-kinase beta is present in the nuclei of NIH 3T3 fibroblasts, suggesting a specific function for this kinase in nuclear processes. ..
  51. Audhya A, Emr S. Stt4 PI 4-kinase localizes to the plasma membrane and functions in the Pkc1-mediated MAP kinase cascade. Dev Cell. 2002;2:593-605 pubmed
    ..Based on these results, we propose that Stt4-Mss4 generates PI4,5P(2) at the plasma membrane, required to recruit/activate effector proteins such as Rom2. ..
  52. Demmel L, Beck M, Klose C, Schlaitz A, Gloor Y, Hsu P, et al. Nucleocytoplasmic shuttling of the Golgi phosphatidylinositol 4-kinase Pik1 is regulated by 14-3-3 proteins and coordinates Golgi function with cell growth. Mol Biol Cell. 2008;19:1046-61 pubmed publisher
    ..These data suggest a role of Pik1p nucleocytoplasmic shuttling in coordination of biosynthetic transport from the Golgi with nutrient signaling. ..
  53. Shelton S, Barylko B, Binns D, Horazdovsky B, Albanesi J, Goodman J. Saccharomyces cerevisiae contains a Type II phosphoinositide 4-kinase. Biochem J. 2003;371:533-40 pubmed
    ..Lsb6p-green fluorescent protein was found both on vacuolar membranes and on the plasma membrane, suggesting a role in endocytic or exocytic pathways. ..