PI4KA explained

Phosphatidylinositol 4-kinase alpha is an enzyme that in humans is encoded by the PI4KA gene.^{[1] [2]}

Function

This gene encodes a 1-phosphatidylinositol 4-kinase which catalyzes the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate. The mammalian PI 4-kinases have been classified into two types, II and III, based on their molecular mass, and modulation by detergent and adenosine. Two transcript variants encoding different isoforms have been described for this gene.^[3]

Clinical significance

The alpha isoform of PI4KIII plays a role in replication of hepatitis C virus (HCV).^[4] Furthermore, the PI4KA lipid kinase affects HCV replication by altering phosphorylation of the HCV NS5A protein.^[5]

Further reading

• Gehrmann T, Heilmeyer LM . Phosphatidylinositol 4-kinases. . Eur. J. Biochem. . 253 . 2 . 357–70 . 1998 . 9654085 . 10.1046/j.1432-1327.1998.2530357.x .
• Graziani A, Ling LE, Endemann G, etal . Purification and characterization of human erythrocyte phosphatidylinositol 4-kinase. Phosphatidylinositol 4-kinase and phosphatidylinositol 3-monophosphate 4-kinase are distinct enzymes . Biochem. J. . 284 . Pt 1. 39–45 . 1992 . 1318025 . 10.1042/bj2840039. 1132694 .
• Kauffmann-Zeh A, Thomas GM, Ball A, etal . Requirement for phosphatidylinositol transfer protein in epidermal growth factor signaling . Science . 268 . 5214 . 1188–90 . 1995 . 7761838 . 10.1126/science.7761838 . 1995Sci...268.1188K .
• Prasad KV, Kapeller R, Janssen O, etal . Phosphatidylinositol (PI) 3-kinase and PI 4-kinase binding to the CD4-p56lck complex: the p56lck SH3 domain binds to PI 3-kinase but not PI 4-kinase . Mol. Cell. Biol. . 13 . 12 . 7708–17 . 1994 . 8246987 . 10.1128/mcb.13.12.7708. 364842 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Res. . 6 . 9 . 791–806 . 1997 . 8889548 . 10.1101/gr.6.9.791 . free .
• Berditchevski F, Chang S, Bodorova J, Hemler ME . Generation of monoclonal antibodies to integrin-associated proteins. Evidence that alpha3beta1 complexes with EMMPRIN/basigin/OX47/M6 . J. Biol. Chem. . 272 . 46 . 29174–80 . 1997 . 9360995 . 10.1074/jbc.272.46.29174 . free .
• Gehrmann T, Gülkan H, Suer S, etal . Functional expression and characterisation of a new human phosphatidylinositol 4-kinase PI4K230 . Biochim. Biophys. Acta . 1437 . 3 . 341–56 . 1999 . 10101268 . 10.1016/s1388-1981(99)00029-3.
• Huang C, Handlogten ME, Miller RT . Parallel activation of phosphatidylinositol 4-kinase and phospholipase C by the extracellular calcium-sensing receptor . J. Biol. Chem. . 277 . 23 . 20293–300 . 2002 . 11907035 . 10.1074/jbc.M200831200 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Subrahmanyam G, Rudd CE, Schneider H . Association of T cell antigen CD7 with type II phosphatidylinositol-4 kinase, a key component in pathways of inositol phosphate turnover . Eur. J. Immunol. . 33 . 1 . 46–52 . 2003 . 12594831 . 10.1002/immu.200390006 . 26388891 . free .
• Carloni V, Mazzocca A, Ravichandran KS . Tetraspanin CD81 is linked to ERK/MAPKinase signaling by Shc in liver tumor cells . Oncogene . 23 . 8 . 1566–74 . 2004 . 14676841 . 10.1038/sj.onc.1207287 . 10393697 .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Ahn J, Chung KS, Kim DU, etal . Systematic identification of hepatocellular proteins interacting with NS5A of the hepatitis C virus . J. Biochem. Mol. Biol. . 37 . 6 . 741–8 . 2005 . 15607035 . 10.5483/bmbrep.2004.37.6.741. free .
• Weixel KM, Blumental-Perry A, Watkins SC, etal . Distinct Golgi populations of phosphatidylinositol 4-phosphate regulated by phosphatidylinositol 4-kinases . J. Biol. Chem. . 280 . 11 . 10501–8 . 2005 . 15634669 . 10.1074/jbc.M414304200 . free .
• Israels SJ, McMillan-Ward EM . CD63 modulates spreading and tyrosine phosphorylation of platelets on immobilized fibrinogen . Thromb. Haemost. . 93 . 2 . 311–8 . 2005 . 15711748 . 10.1160/TH04-08-0503 . 36437042 .
• Waugh MG, Minogue S, Chotai D, etal . Lipid and peptide control of phosphatidylinositol 4-kinase IIalpha activity on Golgi-endosomal Rafts . J. Biol. Chem. . 281 . 7 . 3757–63 . 2006 . 16249177 . 10.1074/jbc.M506527200 . free .
• Israels SJ, McMillan-Ward EM . CD63 modulates spreading and tyrosine phosphorylation of platelets on immobilized fibrinogen . Thromb. Haemost. . 93 . 2 . 311–8 . 2005 . 15711748 . 10.1160/TH04-08-0503 . 36437042 .
• Reiss S, etal . Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment . Cell Host Microbe . 9 . 1 . 32–45 . 2011 . 21238945 . 10.1016/j.chom.2010.12.002 . 3433060.
• Reiss S, etal . The lipid kinase phosphatidylinositol-4 kinase III alpha regulates the phosphorylation status of hepatitis C virus NS5A . PLOS Pathog. . 9 . 5 . e1003359 . 2013 . 23675303 . 10.1371/journal.ppat.1003359 . 3649985 . free .

Notes and References

1. Wong K, Cantley LC . Cloning and characterization of a human phosphatidylinositol 4-kinase . J Biol Chem . 269 . 46 . 28878–84 . Dec 1994 . 10.1016/S0021-9258(19)61989-7 . 7961848 . free .
2. Nakagawa T, Goto K, Kondo H . Cloning, expression, and localization of 230-kDa phosphatidylinositol 4-kinase . J Biol Chem . 271 . 20 . 12088–94 . Aug 1996 . 8662589 . 10.1074/jbc.271.20.12088 . free.
3. Web site: Entrez Gene: PIK4CA phosphatidylinositol 4-kinase, catalytic, alpha polypeptide.
4. Reiss S, Rebhan I, Backes P, Romero-Brey I, Erfle H, Matula P, Kaderali L, Poenisch M, Blankenburg H, Hiet MS, Longerich T, Diehl S, Ramirez F, Balla T, Rohr K, Kaul A, Bühler S, Pepperkok R, Lengauer T, Albrecht M, Eils R, Schirmacher P, Lohmann V, Bartenschlager R . Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment . Cell Host Microbe . 9 . 1 . 32–45 . January 2011 . 21238945 . 3433060 . 10.1016/j.chom.2010.12.002 .
5. Reiss S, Harak C, Romero-Brey I, Radujkovic D, Klein R, Ruggieri A, Rebhan I, Bartenschlager R, Lohmann V . The lipid kinase phosphatidylinositol-4 kinase III alpha regulates the phosphorylation status of hepatitis C virus NS5A . PLOS Pathog. . 9 . 5 . e1003359 . May 2013 . 23675303 . 3649985 . 10.1371/journal.ppat.1003359 . free .