“PI4KB”的意思、由来-开放百科全书

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.

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] In addition, an ALPS motif has been identified in the extreme C-terminal region of PI4KB, which favors its association with unsaturated or loosely packed membranes regions.^[14]

References

1. ^{{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 = February 1997 | pmid = 9020160 | pmc = | doi = 10.1074/jbc.272.7.4384 }}
2. ^{{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 = August 1997 | pmid = 9405938 | pmc = | doi = 10.1093/dnares/4.4.301 }}
3. ^{{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| access-date = }}
4. ^{{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 = April 2002 | pmid = 11950893 }}
5. ^{{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 = September 1999 | pmid = 10559940 | doi = 10.1038/12993 }}
6. ^{{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 = April 2004 | pmid = 14767056 | pmc = 379297 | doi = 10.1091/mbc.E03-12-0862 }}
7. ^{{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 = February 2012 | pmid = 22124328 | pmc = 3273392 | doi = 10.1038/emboj.2011.429 }}
8. ^{{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 | date = April 2013 | pmid = 23572552 | pmc = 3622926 | doi = 10.1128/mBio.00098-13 }}
9. ^{{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 = September 2005 | pmid = 16100512 | pmc = 1458033 | doi = 10.1038/ncb1289 }}
10. ^{{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 = September 2006 | pmid = 16912074 | doi = 10.1242/jcs.03104 }}
11. ^{{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 | pmc = 2982146 | doi = 10.1016/j.cell.2010.03.050 }}
12. ^{{cite journal | vauthors = McNamara CW, Lee MC, Lim CS, Lim SH, Roland J, Simon O, Yeung BK, Chatterjee AK, McCormack SL, Manary MJ, Zeeman AM, Dechering KJ, Kumar TS, Henrich PP, Gagaring K, Ibanez M, Kato N, Kuhen KL, Fischli C, Nagle A, 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 = December 2013 | pmid = 24284631 | pmc = 3940870 | doi = 10.1038/nature12782 }}
13. ^{{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 = 1035–8 | date = May 2014 | pmid = 24876499 | pmc = 4046302 | doi = 10.1126/science.1253397 }}
14. ^{{cite journal | vauthors = Mesmin B, Bigay J, Polidori J, Jamecna D, Lacas-Gervais S, Antonny B | title = Sterol transfer, PI4P consumption, and control of membrane lipid order by endogenous OSBP | journal = The EMBO Journal | volume = 36 | issue = 21 | pages = 3156–3174 | date = November 2017 | pmid = 28978670 | pmc = 5666618 | doi = 10.15252/embj.201796687 }}

Classification

Function

Clinical significance

Structure

References

Further reading