Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Phosphatidylinositol 4-Kinase Type II Alpha

  • Yassmeen Radif
  • Mark G. WaughEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101785


 EC;  Phosphatidylinositol 4-Kinase Type IIα;  PI4K2A;  PI4KIIα;  Type II Phosphatidylinositol 4-Kinase α

Historical Background

Phosphatidylinositol 4-kinase type II α, also commonly referred to as PI4K2A or PI4KIIα, is a 54 kDa lipid kinase that catalyzes the phosphorylation of the membrane lipid phosphatidylinositol on the D4 position of its inositol headgroup to produce phosphatidylinositol 4-phosphate (PI4P). There are three other phosphatidylinositol 4-kinases expressed in most mammalian cells, PI4KB, PI4KA, and PI4KB. PI4K2A is highly homologous to the PI4KB isozyme, and together they are classified as the type II phosphatidylinositol 4-kinases (reviewed in Boura and Nencka 2015; Clayton et al. 2013). The type II phosphatidylinositol kinases differ from the type III PI4KA and PI4KB isozymes in that they are insensitive to the phosphoinositide 3-kinase inhibitors wortmannin and LY-294002, but are inhibited by low micromolar concentrations of adenosine....

This is a preview of subscription content, log in to check access.


  1. Banerji S, Ngo M, Lane CF, Robinson CA, Minogue S, Ridgway ND. Oxysterol binding protein-dependent activation of sphingomyelin synthesis in the golgi apparatus requires phosphatidylinositol 4-kinase IIalpha. Mol Biol Cell. 2010;21:4141–50.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Barylko B, Gerber SH, Binns DD, Grichine N, Khvotchev M, Sudhof TC, Albanesi JP. A novel family of phosphatidylinositol 4-kinases conserved from yeast to humans. J Biol Chem. 2001;276:7705–8.CrossRefPubMedGoogle Scholar
  3. Baumlova A, Chalupska D, Rozycki B, Jovic M, Wisniewski E, Klima M, Dubankova A, Kloer DP, Nencka R, Balla T, Boura E. The crystal structure of the phosphatidylinositol 4-kinase IIalpha. EMBO Rep. 2014;15:1085–92.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Boura E, Nencka R. Phosphatidylinositol 4-kinases: Function, structure, and inhibition. Exp Cell Res. 2015;337:136–45.CrossRefPubMedGoogle Scholar
  5. Chu KM, Minogue S, Hsuan JJ, Waugh MG. Differential effects of the phosphatidylinositol 4-kinases, PI4KIIalpha and PI4KIIIbeta, on Akt activation and apoptosis. Cell Death Dis. 2010;1:e106.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Clayton EL, Minogue S, Waugh MG. Mammalian phosphatidylinositol 4-kinases as modulators of membrane trafficking and lipid signaling networks. Prog Lipid Res. 2013;52:294–304.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Craige B, Salazar G, Faundez V. Phosphatidylinositol-4-kinase type II alpha contains an AP-3 sorting motif and a kinase domain that are both required for endosome traffic. Mol Biol Cell. 2008;19(4):1415–26.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Endemann G, Dunn SN, Cantley LC. Bovine brain contains two types of phosphatidylinositol kinase. Biochemistry. 1987;26:6845–52.CrossRefPubMedGoogle Scholar
  9. Henmi Y, Morikawa Y, Oe N, Ikeda N, Fujita A, Takei K, Minogue S, Tanabe K. PtdIns4KIIalpha generates endosomal PtdIns(4)P and is required for receptor sorting at early endosomes. Mol Biol Cell. 2016;27:990–1001.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Jovic M, Kean MJ, Dubankova A, Boura E, Gingras AC, Brill JA, Balla T. Endosomal sorting of VAMP3 is regulated by PI4K2A. J Cell Sci. 2014;127:3745–56.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Jovic M, Kean MJ, Szentpetery Z, Polevoy G, Gingras AC, Brill JA, Balla T. Two phosphatidylinositol 4-kinases control lysosomal delivery of the Gaucher disease enzyme, beta-glucocerebrosidase. Mol Biol Cell. 2012;23:1533–45.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Ketel K, Krauss M, Nicot AS, Puchkov D, Wieffer M, Muller R, Subramanian D, Schultz C, Laporte J, Haucke V. A phosphoinositide conversion mechanism for exit from endosomes. Nature. 2016;529:408–12.CrossRefPubMedGoogle Scholar
  13. Larimore J, Tornieri K, Ryder PV, Gokhale A, Zlatic SA, Craige B, Lee JD, Talbot K, Pare JF, Smith Y, Faundez V. The schizophrenia susceptibility factor dysbindin and its associated complex sort cargoes from cell bodies to the synapse. Mol Biol Cell. 2011;22:4854–67.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Li J, Lu Y, Zhang J, Kang H, Qin Z, Chen C. PI4KIIalpha is a novel regulator of tumor growth by its action on angiogenesis and HIF-1alpha regulation. Oncogene. 2010;29:2550–9.CrossRefPubMedGoogle Scholar
  15. Lu D, Sun HQ, Wang H, Barylko B, Fukata Y, Fukata M, Albanesi JP, Yin HL. Phosphatidylinositol 4-kinase IIalpha is palmitoylated by Golgi-localized palmitoyltransferases in cholesterol-dependent manner. J Biol Chem. 2012;287:21856–65.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Minogue S, Anderson JS, Waugh MG, dos Santos M, Corless S, Cramer R, Hsuan JJ. Cloning of a human type II phosphatidylinositol 4-kinase reveals a novel lipid kinase family. J Biol Chem. 2001;276:16635–40.CrossRefPubMedGoogle Scholar
  17. Minogue S, Chu KM, Westover EJ, Covey DF, Hsuan JJ, Waugh MG. Relationship between phosphatidylinositol 4-phosphate synthesis, membrane organization, and lateral diffusion of PI4KIIalpha at the trans-Golgi network. J Lipid Res. 2010;51:2314–24.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Minogue S, Waugh MG, De Matteis MA, Stephens DJ, Berditchevski F, Hsuan JJ. Phosphatidylinositol 4-kinase is required for endosomal trafficking and degradation of the EGF receptor. J Cell Sci. 2006;119:571–81.CrossRefPubMedGoogle Scholar
  19. Mossinger J, Wieffer M, Krause E, Freund C, Gerth F, Krauss M, Haucke V. Phosphatidylinositol 4-kinase IIalpha function at endosomes is regulated by the ubiquitin ligase Itch. EMBO Rep. 2012;13(12):1087–94.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Ryder PV, Vistein R, Gokhale A, Seaman MN, Puthenveedu MA, Faundez V. The WASH complex, an endosomal Arp2/3 activator, interacts with the Hermansky-Pudlak syndrome complex BLOC-1 and its cargo phosphatidylinositol-4-kinase type IIalpha. Mol Biol Cell. 2013;24:2269–84.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Simons JP, Al-Shawi R, Minogue S, Waugh MG, Wiedemann C, Evangelou S, Loesch A, Sihra TS, King R, Warner TT, Hsuan JJ. Loss of phosphatidylinositol 4-kinase 2alpha activity causes late onset degeneration of spinal cord axons. Proc Natl Acad Sci U S A. 2009;106:11535–9.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Tai AW, Bojjireddy N, Balla T. A homogeneous and nonisotopic assay for phosphatidylinositol 4-kinases. Anal Biochem. 2011;417:97–102.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Wang J, Sun HQ, Macia E, Kirchhausen T, Watson H, Bonifacino JS, Yin HL. PI4P promotes the recruitment of the GGA adaptor proteins to the trans-Golgi network and regulates their recognition of the ubiquitin sorting signal. Mol Biol Cell. 2007;18:2646–55.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Wang YJ, Wang J, Sun HQ, Martinez M, Sun YX, Macia E, Kirchhausen T, Albanesi JP, Roth MG, Yin HL. Phosphatidylinositol 4 phosphate regulates targeting of clathrin adaptor AP-1 complexes to the Golgi. Cell. 2003;114:299–310.CrossRefPubMedGoogle Scholar
  25. Waugh MG. Chromosomal instability and phosphoinositide pathway gene signatures in glioblastoma multiforme. Mol Neurobiol. 2016;53:621–30.CrossRefPubMedGoogle Scholar
  26. Whitman M, Kaplan D, Roberts T, Cantley L. Evidence for two distinct phosphatidylinositol kinases in fibroblasts. Implications for cellular regulation. Biochem J. 1987;247:165–74.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Wieffer M, Cibrian Uhalte E, Posor Y, Otten C, Branz K, Schutz I, Mossinger J, Schu P, Abdelilah-Seyfried S, Krauss M, Haucke V. PI4K2beta/AP-1-based TGN-endosomal sorting regulates Wnt signaling. Curr Biol. 2013;23:2185–90.CrossRefPubMedGoogle Scholar
  28. Zhou Q, Li J, Yu H, Zhai Y, Gao Z, Liu Y, Pang X, Zhang L, Schulten K, Sun F, Chen C. Molecular insights into the membrane-associated phosphatidylinositol 4-kinase IIalpha. Nat Commun. 2014;5:3552.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Lipid and Membrane Biology Group, Institute for Liver and Digestive Health, Division of MedicineUniversity College LondonLondonUK