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{{Infobox_gene}}
{{PBB_Controls
'''Phosphatidylinositol 4-kinase beta''' is an [[enzyme]] that in humans is encoded by the ''PI4KB'' [[gene]].<ref name="pmid9020160">{{cite journal | vauthors = Meyers R, Cantley LC | title = Cloning and characterization of a wortmannin-sensitive human phosphatidylinositol 4-kinase | journal = The Journal of Biological Chemistry | volume = 272 | issue = 7 | pages = 4384–90 | date = Feb 1997 | pmid = 9020160 | pmc =  | doi = 10.1074/jbc.272.7.4384 }}</ref><ref name="pmid9405938">{{cite journal | vauthors = Saito T, Seki N, Ishii H, Ohira M, Hayashi A, Kozuma S, Hori T | title = Complementary DNA cloning and chromosomal mapping of a novel phosphatidylinositol kinase gene | journal = DNA Research | volume = 4 | issue = 4 | pages = 301–5 | date = Aug 1997 | pmid = 9405938 | pmc = | doi = 10.1093/dnares/4.4.301 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PIK4CB phosphatidylinositol 4-kinase, catalytic, beta polypeptide| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5298| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Classification ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =  
| Name = Phosphatidylinositol 4-kinase, catalytic, beta polypeptide
| HGNCid = 8984
| Symbol = PIK4CB
| AltSymbols =; PI4K-BETA; PI4KIIIbeta; PI4Kbeta
| OMIM = 602758
| ECnumber = 
| Homologene = 6741
| MGIid = 1334433
| GeneAtlas_image1 = PBB_GE_PIK4CB_206139_at_tn.png
| GeneAtlas_image2 = PBB_GE_PIK4CB_206138_s_at_tn.png
| GeneAtlas_image3 = PBB_GE_PIK4CB_210417_s_at_tn.png
| Function = {{GNF_GO|id=GO:0004430 |text = 1-phosphatidylinositol 4-kinase activity}} {{GNF_GO|id=GO:0016301 |text = kinase activity}} {{GNF_GO|id=GO:0016740 |text = transferase activity}} {{GNF_GO|id=GO:0016773 |text = phosphotransferase activity, alcohol group as acceptor}}
| Component = {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005768 |text = endosome}} {{GNF_GO|id=GO:0005783 |text = endoplasmic reticulum}}
| Process = {{GNF_GO|id=GO:0006661 |text = phosphatidylinositol biosynthetic process}} {{GNF_GO|id=GO:0006898 |text = receptor-mediated endocytosis}} {{GNF_GO|id=GO:0007165 |text = signal transduction}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 5298
    | Hs_Ensembl = ENSG00000143393
    | Hs_RefseqProtein = NP_002642
    | Hs_RefseqmRNA = NM_002651
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 1
    | Hs_GenLoc_start = 149531037
    | Hs_GenLoc_end = 149566815
    | Hs_Uniprot = Q9UBF8
    | Mm_EntrezGene = 107650
    | Mm_Ensembl = ENSMUSG00000038861
    | Mm_RefseqmRNA = NM_175356
    | Mm_RefseqProtein = NP_780565
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 3
    | Mm_GenLoc_start = 95060151
    | Mm_GenLoc_end = 95092025
    | Mm_Uniprot = Q14CH6
  }}
}}
'''Phosphatidylinositol 4-kinase, catalytic, beta polypeptide''', also known as '''PIK4CB''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PIK4CB phosphatidylinositol 4-kinase, catalytic, beta polypeptide| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5298| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
This [[gene]] encodes a [[1-phosphatidylinositol 4-kinase|phosphatidylinositol 4-kinase]] which [[catalysis|catalyzes]] [[phosphorylation]] of [[phosphatidylinositol]] at the D-4 position, yielding [[phosphatidylinositol 4-phosphate]] (PI4P). Besides the fact, that [[phosphatidylinositol 4-phosphate|PI4P]] serves as a precursor for other important phosphoinositides, such as [[phosphatidylinositol 4,5-bisphosphate]], [[phosphatidylinositol 4-phosphate|PI4P]] is an essential molecule in the [[cell signaling|cellular signaling]] and trafficking especially in the [[Golgi apparatus]] and the ''trans'' Golgi network.
{{PBB_Summary
| section_title =
| summary_text =
}}


==References==
[[1-phosphatidylinositol 4-kinase|Phosphatidylinositol 4-kinases]] are evolutionary conserved among [[eukaryote]]s and include four human [[protein isoform|isoforms]]
{{reflist|2}}
* [[PI4KA|phosphatidylinositol 4-kinase alpha]] (PI4KA)
==Further reading==
* phosphatidylinositol 4-kinase beta (PI4KB)
{{refbegin | 2}}
* [[PI4K2A|phosphatidylinositol 4-kinase 2-alpha]] (PI4K2A)
{{PBB_Further_reading
* [[PI4K2B|phosphatidylinositol 4-kinase 2-beta]] (PI4K2B)
| citations =
 
*{{cite journal | author=Heilmeyer LM, Vereb G, Vereb G, ''et al.'' |title=Mammalian phosphatidylinositol 4-kinases. |journal=IUBMB Life |volume=55 |issue= 2 |pages= 59-65 |year= 2004 |pmid= 12749687 |doi=  }}
== Function ==
*{{cite journal | author=Meyers R, Cantley LC |title=Cloning and characterization of a wortmannin-sensitive human phosphatidylinositol 4-kinase. |journal=J. Biol. Chem. |volume=272 |issue= 7 |pages= 4384-90 |year= 1997 |pmid= 9020160 |doi= }}
 
*{{cite journal | author=Wong K, Meyers ddR , Cantley LC |title=Subcellular locations of phosphatidylinositol 4-kinase isoforms. |journal=J. Biol. Chem. |volume=272 |issue= 20 |pages= 13236-41 |year= 1997 |pmid= 9148941 |doi= }}
'''Phosphatidylinositol 4-kinase beta (PI4KB)''' is a soluble [[protein]] shuttling between the [[cytoplasm]] and the [[cell nucleus|nucleus]],<ref>{{cite journal | vauthors = de Graaf P, Klapisz EE, Schulz TK, Cremers AF, Verkleij AJ, van Bergen en Henegouwen PM | title = Nuclear localization of phosphatidylinositol 4-kinase beta | journal = Journal of Cell Science | volume = 115 | issue = Pt 8 | pages = 1769–75 | date = Apr 2002 | pmid = 11950893 }}</ref> and can be recruited to the membranes of the [[Golgi apparatus|Golgi system]] via [[protein-protein interaction]]s, e.g. with small [[guanosine triphosphate|GTP]] binding proteins [[ARF1|Arf1]]<ref>{{cite journal | vauthors = Godi A, Pertile P, Meyers R, Marra P, Di Tullio G, Iurisci C, Luini A, Corda D, De Matteis MA | title = ARF mediates recruitment of PtdIns-4-OH kinase-beta and stimulates synthesis of PtdIns(4,5)P2 on the Golgi complex | journal = Nature Cell Biology | volume = 1 | issue = 5 | pages = 280–7 | date = Sep 1999 | pmid = 10559940 | doi = 10.1038/12993 }}</ref> and [[RAB11A|Rab11]],<ref>{{cite journal | vauthors = de Graaf P, Zwart WT, van Dijken RA, Deneka M, Schulz TK, Geijsen N, Coffer PJ, Gadella BM, Verkleij AJ, van der Sluijs P, van Bergen en Henegouwen PM | title = Phosphatidylinositol 4-kinasebeta is critical for functional association of rab11 with the Golgi complex | journal = Molecular Biology of the Cell | volume = 15 | issue = 4 | pages = 2038–47 | date = Apr 2004 | pmid = 14767056 | doi = 10.1091/mbc.E03-12-0862 | pmc=379297}}</ref> or a Golgi adaptor protein [[ACBD3]].<ref>{{cite journal | vauthors = Sasaki J, Ishikawa K, Arita M, Taniguchi K | title = ACBD3-mediated recruitment of PI4KB to picornavirus RNA replication sites | journal = The EMBO Journal | volume = 31 | issue = 3 | pages = 754–66 | date = Feb 2012 | pmid = 22124328 | doi = 10.1038/emboj.2011.429 | pmc=3273392}}</ref><ref>{{cite journal | vauthors = Greninger AL, Knudsen GM, Betegon M, Burlingame AL, DeRisi JL | title = ACBD3 interaction with TBC1 domain 22 protein is differentially affected by enteroviral and kobuviral 3A protein binding | journal = mBio | volume = 4 | issue = 2 | pages = e00098-13–e00098-13 | date = 9 April 2013 | pmid = 23572552 | doi = 10.1128/mBio.00098-13 | pmc=3622926}}</ref> PI4KB can be [[phosphorylation|phosphorylated]] by the [[protein kinase D1|protein kinase D]],<ref>{{cite journal | vauthors = Hausser A, Storz P, Märtens S, Link G, Toker A, Pfizenmaier K | title = Protein kinase D regulates vesicular transport by phosphorylating and activating phosphatidylinositol-4 kinase IIIbeta at the Golgi complex | journal = Nature Cell Biology | volume = 7 | issue = 9 | pages = 880–6 | date = Sep 2005 | pmid = 16100512 | doi = 10.1038/ncb1289 | pmc=1458033}}</ref> which promotes the interaction with [[14-3-3 protein]]s and stabilization of the protein in its active conformation.<ref>{{cite journal | vauthors = Hausser A, Link G, Hoene M, Russo C, Selchow O, Pfizenmaier K | title = Phospho-specific binding of 14-3-3 proteins to phosphatidylinositol 4-kinase III beta protects from dephosphorylation and stabilizes lipid kinase activity | journal = Journal of Cell Science | volume = 119 | issue = Pt 17 | pages = 3613–21 | date = Sep 2006 | pmid = 16912074 | doi = 10.1242/jcs.03104 }}</ref> In [[cytoplasm]] PI4KB regulates the trafficking from the [[Golgi apparatus|Golgi system]] to the [[cell membrane|plasma membrane]], nevertheless, its [[cell nucleus|nuclear]] function remains to be determined.
*{{cite journal | author=Suzuki K, Hirano H, Okutomi K, ''et al.'' |title=Identification and characterization of a novel human phosphatidylinositol 4-kinase. |journal=DNA Res. |volume=4 |issue= 4 |pages= 273-80 |year= 1998 |pmid= 9405935 |doi= }}
 
*{{cite journal | author=Saito T, Seki N, Ishii H, ''et al.'' |title=Complementary DNA cloning and chromosomal mapping of a novel phosphatidylinositol kinase gene. |journal=DNA Res. |volume=4 |issue= 4 |pages= 301-5 |year= 1998 |pmid= 9405938 |doi= }}
== Clinical significance ==
*{{cite journal | author=Sorensen SD, Linseman DA, McEwen EL, ''et al.'' |title=A role for a wortmannin-sensitive phosphatidylinositol-4-kinase in the endocytosis of muscarinic cholinergic receptors. |journal=Mol. Pharmacol. |volume=53 |issue= 5 |pages= 827-36 |year= 1998 |pmid= 9584208 |doi= }}
 
*{{cite journal | author=Godi A, Pertile P, Meyers R, ''et al.'' |title=ARF mediates recruitment of PtdIns-4-OH kinase-beta and stimulates synthesis of PtdIns(4,5)P2 on the Golgi complex. |journal=Nat. Cell Biol. |volume=1 |issue= 5 |pages= 280-7 |year= 1999 |pmid= 10559940 |doi= 10.1038/12993 }}
A wide range of positive-sense single-stranded [[RNA virus]]es (e.g. [[picornavirus]]es) including many important human [[pathogen]]s hijack human PI4KB [[kinase]] to generate specific [[phosphatidylinositol 4-phosphate|PI4P]]-enriched [[organelle]]s called membranous webs.<ref>{{cite journal | vauthors = Hsu NY, Ilnytska O, Belov G, Santiana M, Chen YH, Takvorian PM, Pau C, van der Schaar H, Kaushik-Basu N, Balla T, Cameron CE, Ehrenfeld E, van Kuppeveld FJ, Altan-Bonnet N | title = Viral reorganization of the secretory pathway generates distinct organelles for RNA replication | journal = Cell | volume = 141 | issue = 5 | pages = 799–811 | date = May 2010 | pmid = 20510927 | doi = 10.1016/j.cell.2010.03.050 | pmc=2982146}}</ref> These [[organelle]]s are then used as specific platforms for the effective [[viral replication]] within the host cell.
*{{cite journal  | author=Suer S, Sickmann A, Meyer HE, ''et al.'' |title=Human phosphatidylinositol 4-kinase isoform PI4K92. Expression of the recombinant enzyme and determination of multiple phosphorylation sites. |journal=Eur. J. Biochem. |volume=268 |issue= 7 |pages= 2099-106 |year= 2001 |pmid= 11277933 |doi=  }}
 
*{{cite journal | author=Zhao X, Várnai P, Tuymetova G, ''et al.'' |title=Interaction of neuronal calcium sensor-1 (NCS-1) with phosphatidylinositol 4-kinase beta stimulates lipid kinase activity and affects membrane trafficking in COS-7 cells. |journal=J. Biol. Chem. |volume=276 |issue= 43 |pages= 40183-9 |year= 2001 |pmid= 11526106 |doi= 10.1074/jbc.M104048200 }}
Furthermore, PI4KB homologue from the [[protozoa]]n [[parasite]] [[Plasmodium falciparum]] has been identified as a target of imidopyrazines, an [[malaria|antimalarial]] compound class.<ref>{{cite journal | vauthors = McNamara CW, Lee MC, Lim CS, Lim SH, Roland J, Nagle A, Simon O, Yeung BK, Chatterjee AK, McCormack SL, Manary MJ, Zeeman AM, Dechering KJ, Kumar TR, Henrich PP, Gagaring K, Ibanez M, Kato N, Kuhen KL, Fischli C, Rottmann M, Plouffe DM, Bursulaya B, Meister S, Rameh L, Trappe J, Haasen D, Timmerman M, Sauerwein RW, Suwanarusk R, Russell B, Renia L, Nosten F, Tully DC, Kocken CH, Glynne RJ, Bodenreider C, Fidock DA, Diagana TT, Winzeler EA | title = Targeting Plasmodium PI(4)K to eliminate malaria | journal = Nature | volume = 504 | issue = 7479 | pages = 248–253 | date = Dec 2013 | pmid = 24284631 | doi = 10.1038/nature12782 | pmc=3940870}}</ref>
*{{cite journal | author=Balla A, Tuymetova G, Barshishat M, ''et al.'' |title=Characterization of type II phosphatidylinositol 4-kinase isoforms reveals association of the enzymes with endosomal vesicular compartments. |journal=J. Biol. Chem. |volume=277 |issue= 22 |pages= 20041-50 |year= 2002 |pmid= 11923287 |doi= 10.1074/jbc.M111807200 }}
 
*{{cite journal  | author=Taverna E, Francolini M, Jeromin A, ''et al.'' |title=Neuronal calcium sensor 1 and phosphatidylinositol 4-OH kinase beta interact in neuronal cells and are translocated to membranes during nucleotide-evoked exocytosis. |journal=J. Cell. Sci. |volume=115 |issue= Pt 20 |pages= 3909-22 |year= 2003 |pmid= 12244129 |doi=  }}
== Structure ==
*{{cite journal | author=Wei YJ, Sun HQ, Yamamoto M, ''et al.'' |title=Type II phosphatidylinositol 4-kinase beta is a cytosolic and peripheral membrane protein that is recruited to the plasma membrane and activated by Rac-GTP. |journal=J. Biol. Chem. |volume=277 |issue= 48 |pages= 46586-93 |year= 2003 |pmid= 12324459 |doi= 10.1074/jbc.M206860200 }}
 
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
PI4KB is composed of a [[proline]]-rich ''N''-terminal region, a central helical domain, and a [[kinase]] domain located ''C''-terminally. The ''N''-terminal region contains a physiologically important binding site for a Golgi adaptor protein [[ACBD3]], but is likely disordered and dispensable for the [[kinase]] activity. The central helical domain is responsible for the interaction with a small guanosine triphosphatase [[RAB11A|Rab11]]. The [[kinase]] domain can be divided into ''N''-terminal and ''C''-terminal lobes with the [[adenosine triphosphate|ATP]] binding groove and putative [[phosphatidylinositol]] binding pocket in a cleft between the lobes.<ref>{{cite journal | vauthors = Burke JE, Inglis AJ, Perisic O, Masson GR, McLaughlin SH, Rutaganira F, Shokat KM, Williams RL | title = Structures of PI4KIIIβ complexes show simultaneous recruitment of Rab11 and its effectors | journal = Science | volume = 344 | issue = 6187 | pages = 1035–1038 | date = May 2014 | pmid = 24876499 | doi = 10.1126/science.1253397 | pmc=4046302}}</ref>
*{{cite journal | author=Kapp-Barnea Y, Melnikov S, Shefler I, ''et al.'' |title=Neuronal calcium sensor-1 and phosphatidylinositol 4-kinase beta regulate IgE receptor-triggered exocytosis in cultured mast cells. |journal=J. Immunol. |volume=171 |issue= 10 |pages= 5320-7 |year= 2004 |pmid= 14607934 |doi= }}
 
*{{cite journal | author=Jin J, Smith FD, Stark C, ''et al.'' |title=Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization. |journal=Curr. Biol. |volume=14 |issue= 16 |pages= 1436-50 |year= 2004 |pmid= 15324660 |doi= 10.1016/j.cub.2004.07.051 }}
[[Image:PI4KB.png|thumb|325 px|'''Cartoon representation of the helical and kinase domains of the phosphatidylinositol 4-kinase beta with a nucleoside analogue.''' Helical domain is colored in salmon, ''N''-lobe of the kinase domain in gold, ''C''-lobe in aquamarine, a specific inhibitor bound in the active site between the lobes in the stick representation. PDB code: 4WAG.]]
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
 
*{{cite journal | author=Weixel KM, Blumental-Perry A, Watkins SC, ''et al.'' |title=Distinct Golgi populations of phosphatidylinositol 4-phosphate regulated by phosphatidylinositol 4-kinases. |journal=J. Biol. Chem. |volume=280 |issue= 11 |pages= 10501-8 |year= 2005 |pmid= 15634669 |doi= 10.1074/jbc.M414304200 }}
== References ==
*{{cite journal | author=Benzinger A, Muster N, Koch HB, ''et al.'' |title=Targeted proteomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer. |journal=Mol. Cell Proteomics |volume=4 |issue= 6 |pages= 785-95 |year= 2005 |pmid= 15778465 |doi= 10.1074/mcp.M500021-MCP200 }}
{{reflist}}
*{{cite journal | author=Rual JF, Venkatesan K, Hao T, ''et al.'' |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173-8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 }}
 
}}
== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Balla A, Balla T | title = Phosphatidylinositol 4-kinases: old enzymes with emerging functions | journal = Trends in Cell Biology | volume = 16 | issue = 7 | pages = 351–61 | date = Jul 2006 | pmid = 16793271 | doi = 10.1016/j.tcb.2006.05.003 }}
* {{cite journal | vauthors = Balla T | title = Phosphoinositides: tiny lipids with giant impact on cell regulation | journal = Physiological Reviews | volume = 93 | issue = 3 | pages = 1019–137 | date = Jul 2013 | pmid = 23899561 | doi = 10.1152/physrev.00028.2012 | pmc=3962547}}
* {{cite journal | vauthors = Altan-Bonnet N, Balla T | title = Phosphatidylinositol 4-kinases: hostages harnessed to build panviral replication platforms | journal = Trends in Biochemical Sciences | volume = 37 | issue = 7 | pages = 293–302 | date = Jul 2012 | pmid = 22633842 | doi = 10.1016/j.tibs.2012.03.004 | pmc=3389303}}
* {{cite journal | vauthors = Minogue S, Waugh MG | title = The phosphatidylinositol 4-kinases: don't call it a comeback | journal = Sub-Cellular Biochemistry | volume = 58 | pages = 1–24 | date = 2012 | pmid = 22403072 | doi = 10.1007/978-94-007-3012-0_1 }}
* {{cite journal | vauthors = Kutateladze TG | title = Translation of the phosphoinositide code by PI effectors | journal = Nature Chemical Biology | volume = 6 | issue = 7 | pages = 507–13 | date = Jul 2010 | pmid = 20559318 | doi = 10.1038/nchembio.390 | pmc=3182472}}
* {{cite journal | vauthors = Tan J, Brill JA | title = Cinderella story: PI4P goes from precursor to key signaling molecule | journal = Critical Reviews in Biochemistry and Molecular Biology | volume = 49 | issue = 1 | pages = 33–58 | date = 2014 | pmid = 24219382 | doi = 10.3109/10409238.2013.853024 }}
{{refend}}
{{refend}}
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Revision as of 18:05, 7 September 2017

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Phosphatidylinositol 4-kinase beta is an enzyme that in humans is encoded by the PI4KB gene.[1][2][3]

Classification

This gene encodes a phosphatidylinositol 4-kinase which catalyzes phosphorylation of phosphatidylinositol at the D-4 position, yielding phosphatidylinositol 4-phosphate (PI4P). Besides the fact, that PI4P serves as a precursor for other important phosphoinositides, such as phosphatidylinositol 4,5-bisphosphate, PI4P is an essential molecule in the cellular signaling and trafficking especially in the Golgi apparatus and the trans Golgi network.

Phosphatidylinositol 4-kinases are evolutionary conserved among eukaryotes and include four human isoforms

Function

Phosphatidylinositol 4-kinase beta (PI4KB) is a soluble protein shuttling between the cytoplasm and the nucleus,[4] and can be recruited to the membranes of the Golgi system via protein-protein interactions, e.g. with small GTP binding proteins Arf1[5] and Rab11,[6] or a Golgi adaptor protein ACBD3.[7][8] PI4KB can be phosphorylated by the protein kinase D,[9] which promotes the interaction with 14-3-3 proteins and stabilization of the protein in its active conformation.[10] In cytoplasm PI4KB regulates the trafficking from the Golgi system to the plasma membrane, nevertheless, its nuclear function remains to be determined.

Clinical significance

A wide range of positive-sense single-stranded RNA viruses (e.g. picornaviruses) including many important human pathogens hijack human PI4KB kinase to generate specific PI4P-enriched organelles called membranous webs.[11] These organelles are then used as specific platforms for the effective viral replication within the host cell.

Furthermore, PI4KB homologue from the protozoan parasite Plasmodium falciparum has been identified as a target of imidopyrazines, an antimalarial compound class.[12]

Structure

PI4KB is composed of a proline-rich N-terminal region, a central helical domain, and a kinase domain located C-terminally. The N-terminal region contains a physiologically important binding site for a Golgi adaptor protein ACBD3, but is likely disordered and dispensable for the kinase activity. The central helical domain is responsible for the interaction with a small guanosine triphosphatase Rab11. The kinase domain can be divided into N-terminal and C-terminal lobes with the ATP binding groove and putative phosphatidylinositol binding pocket in a cleft between the lobes.[13]

File:PI4KB.png
Cartoon representation of the helical and kinase domains of the phosphatidylinositol 4-kinase beta with a nucleoside analogue. Helical domain is colored in salmon, N-lobe of the kinase domain in gold, C-lobe in aquamarine, a specific inhibitor bound in the active site between the lobes in the stick representation. PDB code: 4WAG.

References

  1. ↑ Meyers R, Cantley LC (Feb 1997). "Cloning and characterization of a wortmannin-sensitive human phosphatidylinositol 4-kinase". The Journal of Biological Chemistry. 272 (7): 4384–90. doi:10.1074/jbc.272.7.4384. PMID 9020160.
  2. ↑ Saito T, Seki N, Ishii H, Ohira M, Hayashi A, Kozuma S, Hori T (Aug 1997). "Complementary DNA cloning and chromosomal mapping of a novel phosphatidylinositol kinase gene". DNA Research. 4 (4): 301–5. doi:10.1093/dnares/4.4.301. PMID 9405938.
  3. ↑ "Entrez Gene: PIK4CB phosphatidylinositol 4-kinase, catalytic, beta polypeptide".
  4. ↑ de Graaf P, Klapisz EE, Schulz TK, Cremers AF, Verkleij AJ, van Bergen en Henegouwen PM (Apr 2002). "Nuclear localization of phosphatidylinositol 4-kinase beta". Journal of Cell Science. 115 (Pt 8): 1769–75. PMID 11950893.
  5. ↑ Godi A, Pertile P, Meyers R, Marra P, Di Tullio G, Iurisci C, Luini A, Corda D, De Matteis MA (Sep 1999). "ARF mediates recruitment of PtdIns-4-OH kinase-beta and stimulates synthesis of PtdIns(4,5)P2 on the Golgi complex". Nature Cell Biology. 1 (5): 280–7. doi:10.1038/12993. PMID 10559940.
  6. ↑ de Graaf P, Zwart WT, van Dijken RA, Deneka M, Schulz TK, Geijsen N, Coffer PJ, Gadella BM, Verkleij AJ, van der Sluijs P, van Bergen en Henegouwen PM (Apr 2004). "Phosphatidylinositol 4-kinasebeta is critical for functional association of rab11 with the Golgi complex". Molecular Biology of the Cell. 15 (4): 2038–47. doi:10.1091/mbc.E03-12-0862. PMC 379297. PMID 14767056.
  7. ↑ Sasaki J, Ishikawa K, Arita M, Taniguchi K (Feb 2012). "ACBD3-mediated recruitment of PI4KB to picornavirus RNA replication sites". The EMBO Journal. 31 (3): 754–66. doi:10.1038/emboj.2011.429. PMC 3273392. PMID 22124328.
  8. ↑ Greninger AL, Knudsen GM, Betegon M, Burlingame AL, DeRisi JL (9 April 2013). "ACBD3 interaction with TBC1 domain 22 protein is differentially affected by enteroviral and kobuviral 3A protein binding". mBio. 4 (2): e00098–13–e00098–13. doi:10.1128/mBio.00098-13. PMC 3622926. PMID 23572552.
  9. ↑ Hausser A, Storz P, Märtens S, Link G, Toker A, Pfizenmaier K (Sep 2005). "Protein kinase D regulates vesicular transport by phosphorylating and activating phosphatidylinositol-4 kinase IIIbeta at the Golgi complex". Nature Cell Biology. 7 (9): 880–6. doi:10.1038/ncb1289. PMC 1458033. PMID 16100512.
  10. ↑ Hausser A, Link G, Hoene M, Russo C, Selchow O, Pfizenmaier K (Sep 2006). "Phospho-specific binding of 14-3-3 proteins to phosphatidylinositol 4-kinase III beta protects from dephosphorylation and stabilizes lipid kinase activity". Journal of Cell Science. 119 (Pt 17): 3613–21. doi:10.1242/jcs.03104. PMID 16912074.
  11. ↑ Hsu NY, Ilnytska O, Belov G, Santiana M, Chen YH, Takvorian PM, Pau C, van der Schaar H, Kaushik-Basu N, Balla T, Cameron CE, Ehrenfeld E, van Kuppeveld FJ, Altan-Bonnet N (May 2010). "Viral reorganization of the secretory pathway generates distinct organelles for RNA replication". Cell. 141 (5): 799–811. doi:10.1016/j.cell.2010.03.050. PMC 2982146. PMID 20510927.
  12. ↑ McNamara CW, Lee MC, Lim CS, Lim SH, Roland J, Nagle A, Simon O, Yeung BK, Chatterjee AK, McCormack SL, Manary MJ, Zeeman AM, Dechering KJ, Kumar TR, Henrich PP, Gagaring K, Ibanez M, Kato N, Kuhen KL, Fischli C, Rottmann M, Plouffe DM, Bursulaya B, Meister S, Rameh L, Trappe J, Haasen D, Timmerman M, Sauerwein RW, Suwanarusk R, Russell B, Renia L, Nosten F, Tully DC, Kocken CH, Glynne RJ, Bodenreider C, Fidock DA, Diagana TT, Winzeler EA (Dec 2013). "Targeting Plasmodium PI(4)K to eliminate malaria". Nature. 504 (7479): 248–253. doi:10.1038/nature12782. PMC 3940870. PMID 24284631.
  13. ↑ Burke JE, Inglis AJ, Perisic O, Masson GR, McLaughlin SH, Rutaganira F, Shokat KM, Williams RL (May 2014). "Structures of PI4KIIIβ complexes show simultaneous recruitment of Rab11 and its effectors". Science. 344 (6187): 1035–1038. doi:10.1126/science.1253397. PMC 4046302. PMID 24876499.

Further reading

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