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Pathway Description
Phosphatidylinositol Phosphate Metabolism
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2013-08-19
Last Updated: 2023-10-25
Phosphatidylinositol phosphates, or phosphoinositides, are intracellular signaling lipids. Seven different phosphoinositides have been identified in mammals, each distinguished by the number and/or position of the phosphate groups on the inositol ring. The inositol can be mono-, di-, or triphosphorylated, with the remaining phosphoinositides being isomers of these three forms. Phosphoinositides regulate a variety of signal transduction processes, thus playing a number of important roles in the cell, such as actin cytoskeletal reorganization, membrane transport, and cell proliferation. They may also affect protein localization, aggregation, and activity by acting as secondary messengers. The ability of the cell to recognize the different types of phosphoinositides as different cellular signals means that their synthesis and metabolism must be tightly regulated. Synthesis begins with the attachment of an inositol phosphate head group to diacylglycerol via a phospholipase C enzyme, creating a phosphoinositide. Conversion between the different types of phosphoinositides is then done by a number of specific phosphoinositide kinases and phosphatases, which add (kinase) and remove (phosphatase) phosphates from the inositol ring. The specific localization and regulation of the phosphoinositide kinases and phosphatases thus controls the activity of the phosphoinositides. While the phosphoinositides are always located in the membrane, their particular kinases and phosphatases may be found in the cytoplasm or in the membrane of the cell or cell organelles.
References
Phosphatidylinositol Phosphate Metabolism References
Abel K, Anderson RA, Shears SB: Phosphatidylinositol and inositol phosphate metabolism. J Cell Sci. 2001 Jun;114(Pt 12):2207-8.
Pubmed: 11493657
Anderson RA, Boronenkov IV, Doughman SD, Kunz J, Loijens JC: Phosphatidylinositol phosphate kinases, a multifaceted family of signaling enzymes. J Biol Chem. 1999 Apr 9;274(15):9907-10.
Pubmed: 10187762
De Matteis MA, Di Campli A, Godi A: The role of the phosphoinositides at the Golgi complex. Biochim Biophys Acta. 2005 Jul 10;1744(3):396-405. doi: 10.1016/j.bbamcr.2005.04.013.
Pubmed: 15979509
Giudici ML, Hinchliffe KA, Irvine RF: Phosphatidylinositol phosphate kinases. J Endocrinol Invest. 2004;27(6 Suppl):137-42.
Pubmed: 15481814
Kanaho Y, Suzuki T: Phosphoinositide kinases as enzymes that produce versatile signaling lipids, phosphoinositides. J Biochem. 2002 Apr;131(4):503-9.
Pubmed: 11926986
Poccia D, Larijani B: Phosphatidylinositol metabolism and membrane fusion. Biochem J. 2009 Mar 1;418(2):233-46. doi: 10.1042/BJ20082105.
Pubmed: 19196244
Sasaki T, Takasuga S, Sasaki J, Kofuji S, Eguchi S, Yamazaki M, Suzuki A: Mammalian phosphoinositide kinases and phosphatases. Prog Lipid Res. 2009 Nov;48(6):307-43. doi: 10.1016/j.plipres.2009.06.001. Epub 2009 Jul 4.
Pubmed: 19580826
Vanhaesebroeck B, Leevers SJ, Ahmadi K, Timms J, Katso R, Driscoll PC, Woscholski R, Parker PJ, Waterfield MD: Synthesis and function of 3-phosphorylated inositol lipids. Annu Rev Biochem. 2001;70:535-602. doi: 10.1146/annurev.biochem.70.1.535.
Pubmed: 11395417
Lykidis A, Jackson PD, Rock CO, Jackowski S: The role of CDP-diacylglycerol synthetase and phosphatidylinositol synthase activity levels in the regulation of cellular phosphatidylinositol content. J Biol Chem. 1997 Dec 26;272(52):33402-9. doi: 10.1074/jbc.272.52.33402.
Pubmed: 9407135
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Martin J, Han C, Gordon LA, Terry A, Prabhakar S, She X, Xie G, Hellsten U, Chan YM, Altherr M, Couronne O, Aerts A, Bajorek E, Black S, Blumer H, Branscomb E, Brown NC, Bruno WJ, Buckingham JM, Callen DF, Campbell CS, Campbell ML, Campbell EW, Caoile C, Challacombe JF, Chasteen LA, Chertkov O, Chi HC, Christensen M, Clark LM, Cohn JD, Denys M, Detter JC, Dickson M, Dimitrijevic-Bussod M, Escobar J, Fawcett JJ, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Goodwin LA, Grady DL, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Hildebrand CE, Huang W, Israni S, Jett J, Jewett PB, Kadner K, Kimball H, Kobayashi A, Krawczyk MC, Leyba T, Longmire JL, Lopez F, Lou Y, Lowry S, Ludeman T, Manohar CF, Mark GA, McMurray KL, Meincke LJ, Morgan J, Moyzis RK, Mundt MO, Munk AC, Nandkeshwar RD, Pitluck S, Pollard M, Predki P, Parson-Quintana B, Ramirez L, Rash S, Retterer J, Ricke DO, Robinson DL, Rodriguez A, Salamov A, Saunders EH, Scott D, Shough T, Stallings RL, Stalvey M, Sutherland RD, Tapia R, Tesmer JG, Thayer N, Thompson LS, Tice H, Torney DC, Tran-Gyamfi M, Tsai M, Ulanovsky LE, Ustaszewska A, Vo N, White PS, Williams AL, Wills PL, Wu JR, Wu K, Yang J, Dejong P, Bruce D, Doggett NA, Deaven L, Schmutz J, Grimwood J, Richardson P, Rokhsar DS, Eichler EE, Gilna P, Lucas SM, Myers RM, Rubin EM, Pennacchio LA: The sequence and analysis of duplication-rich human chromosome 16. Nature. 2004 Dec 23;432(7020):988-94. doi: 10.1038/nature03187.
Pubmed: 15616553
Krebs CE, Karkheiran S, Powell JC, Cao M, Makarov V, Darvish H, Di Paolo G, Walker RH, Shahidi GA, Buxbaum JD, De Camilli P, Yue Z, Paisan-Ruiz C: The Sac1 domain of SYNJ1 identified mutated in a family with early-onset progressive Parkinsonism with generalized seizures. Hum Mutat. 2013 Sep;34(9):1200-7. doi: 10.1002/humu.22372. Epub 2013 Jul 19.
Pubmed: 23804563
Haffner C, Takei K, Chen H, Ringstad N, Hudson A, Butler MH, Salcini AE, Di Fiore PP, De Camilli P: Synaptojanin 1: localization on coated endocytic intermediates in nerve terminals and interaction of its 170 kDa isoform with Eps15. FEBS Lett. 1997 Dec 15;419(2-3):175-80. doi: 10.1016/s0014-5793(97)01451-8.
Pubmed: 9428629
Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 1998 Dec 31;5(6):355-64. doi: 10.1093/dnares/5.6.355.
Pubmed: 10048485
Volinia S, Hiles I, Ormondroyd E, Nizetic D, Antonacci R, Rocchi M, Waterfield MD: Molecular cloning, cDNA sequence, and chromosomal localization of the human phosphatidylinositol 3-kinase p110 alpha (PIK3CA) gene. Genomics. 1994 Dec;24(3):472-7.
Pubmed: 7713498
Rodriguez-Laguna L, Ibanez K, Gordo G, Garcia-Minaur S, Santos-Simarro F, Agra N, Vallespin E, Fernandez-Montano VE, Martin-Arenas R, Del Pozo A, Gonzalez-Pecellin H, Mena R, Rueda-Arenas I, Gomez MV, Villaverde C, Bustamante A, Ayuso C, Ruiz-Perez VL, Nevado J, Lapunzina P, Lopez-Gutierrez JC, Martinez-Glez V: CLAPO syndrome: identification of somatic activating PIK3CA mutations and delineation of the natural history and phenotype. Genet Med. 2018 Aug;20(8):882-889. doi: 10.1038/gim.2017.200. Epub 2018 Feb 15.
Pubmed: 29446767
Campbell IG, Russell SE, Choong DY, Montgomery KG, Ciavarella ML, Hooi CS, Cristiano BE, Pearson RB, Phillips WA: Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res. 2004 Nov 1;64(21):7678-81. doi: 10.1158/0008-5472.CAN-04-2933.
Pubmed: 15520168
Skolnik EY, Margolis B, Mohammadi M, Lowenstein E, Fischer R, Drepps A, Ullrich A, Schlessinger J: Cloning of PI3 kinase-associated p85 utilizing a novel method for expression/cloning of target proteins for receptor tyrosine kinases. Cell. 1991 Apr 5;65(1):83-90. doi: 10.1016/0092-8674(91)90410-z.
Pubmed: 1849461
Antonetti DA, Algenstaedt P, Kahn CR: Insulin receptor substrate 1 binds two novel splice variants of the regulatory subunit of phosphatidylinositol 3-kinase in muscle and brain. Mol Cell Biol. 1996 May;16(5):2195-203. doi: 10.1128/mcb.16.5.2195.
Pubmed: 8628286
Volinia S, Dhand R, Vanhaesebroeck B, MacDougall LK, Stein R, Zvelebil MJ, Domin J, Panaretou C, Waterfield MD: A human phosphatidylinositol 3-kinase complex related to the yeast Vps34p-Vps15p protein sorting system. EMBO J. 1995 Jul 17;14(14):3339-48.
Pubmed: 7628435
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Stein MP, Feng Y, Cooper KL, Welford AM, Wandinger-Ness A: Human VPS34 and p150 are Rab7 interacting partners. Traffic. 2003 Nov;4(11):754-71.
Pubmed: 14617358
Panaretou C, Domin J, Cockcroft S, Waterfield MD: Characterization of p150, an adaptor protein for the human phosphatidylinositol (PtdIns) 3-kinase. Substrate presentation by phosphatidylinositol transfer protein to the p150.Ptdins 3-kinase complex. J Biol Chem. 1997 Jan 24;272(4):2477-85. doi: 10.1074/jbc.272.4.2477.
Pubmed: 8999962
Fimia GM, Stoykova A, Romagnoli A, Giunta L, Di Bartolomeo S, Nardacci R, Corazzari M, Fuoco C, Ucar A, Schwartz P, Gruss P, Piacentini M, Chowdhury K, Cecconi F: Ambra1 regulates autophagy and development of the nervous system. Nature. 2007 Jun 28;447(7148):1121-5. doi: 10.1038/nature05925. Epub 2007 Jun 24.
Pubmed: 17589504
Nagase T, Kikuno R, Hattori A, Kondo Y, Okumura K, Ohara O: Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 2000 Dec 31;7(6):347-55. doi: 10.1093/dnares/7.6.347.
Pubmed: 11214970
Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. doi: 10.1038/nature03466.
Pubmed: 15815621
Chow CY, Landers JE, Bergren SK, Sapp PC, Grant AE, Jones JM, Everett L, Lenk GM, McKenna-Yasek DM, Weisman LS, Figlewicz D, Brown RH, Meisler MH: Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS. Am J Hum Genet. 2009 Jan;84(1):85-8. doi: 10.1016/j.ajhg.2008.12.010.
Pubmed: 19118816
Nicholson G, Lenk GM, Reddel SW, Grant AE, Towne CF, Ferguson CJ, Simpson E, Scheuerle A, Yasick M, Hoffman S, Blouin R, Brandt C, Coppola G, Biesecker LG, Batish SD, Meisler MH: Distinctive genetic and clinical features of CMT4J: a severe neuropathy caused by mutations in the PI(3,5)P(2) phosphatase FIG4. Brain. 2011 Jul;134(Pt 7):1959-71. doi: 10.1093/brain/awr148.
Pubmed: 21705420
Baulac S, Lenk GM, Dufresnois B, Ouled Amar Bencheikh B, Couarch P, Renard J, Larson PA, Ferguson CJ, Noe E, Poirier K, Hubans C, Ferreira S, Guerrini R, Ouazzani R, El Hachimi KH, Meisler MH, Leguern E: Role of the phosphoinositide phosphatase FIG4 gene in familial epilepsy with polymicrogyria. Neurology. 2014 Mar 25;82(12):1068-75. doi: 10.1212/WNL.0000000000000241. Epub 2014 Mar 5.
Pubmed: 24598713
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