Inositol phosphates (IPs) are molecules involves in signalling processes in eukaryotes. myo-Inositol consists of a six-carbon cyclic alcohol with an axial 2-hydroxy and five equatorial hydroxyls. Mono-, di-, and triphosphorylation of the inositol ring generates a wide variety of stereochemically distinct signalling entities. Inositol 1,4,5-trisphosphate (I(1,4,5)P3), is formed when the phosphoinositide phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is hydrolysed by a phospholipase C isozyme. An array of inositol trisphosphate (IP3) and tetrakisphosphate (IP4) molecules are synthesised by the action of various kinases and phosphatases in the cytosol. These species then transport between the cytosol and the nucleus where they are acted on by inositol polyphosphate multikinase (IPMK), inositol-pentakisphosphate 2-kinase (IPPK), inositol hexakisphosphate kinase 1 (IP6K1) and 2 (IP6K2), to produce IP5, IP6, IP7, and IP8 molecules. Some of these nuclear produced IPs transport back to the cytosol where they are converted to an even wider variety of IPs, by kinases and phosphatases, including the di- and triphospho inositol phosphates aka pyrophosphates (Irvine & Schell 2001, Bunney & Katan 2010, Alcazar-Romain & Wente 2008, York 2006, Monserrate and York 2010).
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Drayer AL, Pesesse X, De Smedt F, Woscholski R, Parker P, Erneux C.; ''Cloning and expression of a human placenta inositol 1,3,4,5-tetrakisphosphate and phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase.''; PubMedEurope PMCScholia
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Yang X, Shears SB.; ''Multitasking in signal transduction by a promiscuous human Ins(3,4,5,6)P(4) 1-kinase/Ins(1,3,4)P(3) 5/6-kinase.''; PubMedEurope PMCScholia
Carozzi AJ, Kriz RW, Webster C, Parker PJ.; ''Identification, purification and characterization of a novel phosphatidylinositol-specific phospholipase C, a third member of the beta subfamily.''; PubMedEurope PMCScholia
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Leung DW, Tompkins C, Brewer J, Ball A, Coon M, Morris V, Waggoner D, Singer JW.; ''Phospholipase C delta-4 overexpression upregulates ErbB1/2 expression, Erk signaling pathway, and proliferation in MCF-7 cells.''; PubMedEurope PMCScholia
Chang SC, Miller AL, Feng Y, Wente SR, Majerus PW.; ''The human homolog of the rat inositol phosphate multikinase is an inositol 1,3,4,6-tetrakisphosphate 5-kinase.''; PubMedEurope PMCScholia
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Bunney TD, Katan M.; ''Phosphoinositide signalling in cancer: beyond PI3K and PTEN.''; PubMedEurope PMCScholia
Banno Y, Yada Y, Nozawa Y.; ''Purification and characterization of membrane-bound phospholipase C specific for phosphoinositides from human platelets.''; PubMedEurope PMCScholia
Cheng HF, Jiang MJ, Chen CL, Liu SM, Wong LP, Lomasney JW, King K.; ''Cloning and identification of amino acid residues of human phospholipase C delta 1 essential for catalysis.''; PubMedEurope PMCScholia
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Ho MW, Yang X, Carew MA, Zhang T, Hua L, Kwon YU, Chung SK, Adelt S, Vogel G, Riley AM, Potter BV, Shears SB.; ''Regulation of Ins(3,4,5,6)P(4) signaling by a reversible kinase/phosphatase.''; PubMedEurope PMCScholia
Caricasole A, Sala C, Roncarati R, Formenti E, Terstappen GC.; ''Cloning and characterization of the human phosphoinositide-specific phospholipase C-beta 1 (PLC beta 1).''; PubMedEurope PMCScholia
Chi Y, Zhou B, Wang WQ, Chung SK, Kwon YU, Ahn YH, Chang YT, Tsujishita Y, Hurley JH, Zhang ZY.; ''Comparative mechanistic and substrate specificity study of inositol polyphosphate 5-phosphatase Schizosaccharomyces pombe Synaptojanin and SHIP2.''; PubMedEurope PMCScholia
Thorsell AG, Persson C, Voevodskaya N, Busam RD, Hammarström M, Gräslund S, Gräslund A, Hallberg BM.; ''Structural and biophysical characterization of human myo-inositol oxygenase.''; PubMedEurope PMCScholia
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Lin H, Fridy PC, Ribeiro AA, Choi JH, Barma DK, Vogel G, Falck JR, Shears SB, York JD, Mayr GW.; ''Structural analysis and detection of biological inositol pyrophosphates reveal that the family of VIP/diphosphoinositol pentakisphosphate kinases are 1/3-kinases.''; PubMedEurope PMCScholia
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Norris FA, Auethavekiat V, Majerus PW.; ''The isolation and characterization of cDNA encoding human and rat brain inositol polyphosphate 4-phosphatase.''; PubMedEurope PMCScholia
Draskovic P, Saiardi A, Bhandari R, Burton A, Ilc G, Kovacevic M, Snyder SH, Podobnik M.; ''Inositol hexakisphosphate kinase products contain diphosphate and triphosphate groups.''; PubMedEurope PMCScholia
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McAllister G, Whiting P, Hammond EA, Knowles MR, Atack JR, Bailey FJ, Maigetter R, Ragan CI.; ''cDNA cloning of human and rat brain myo-inositol monophosphatase. Expression and characterization of the human recombinant enzyme.''; PubMedEurope PMCScholia
Zhang X, Hartz PA, Philip E, Racusen LC, Majerus PW.; ''Cell lines from kidney proximal tubules of a patient with Lowe syndrome lack OCRL inositol polyphosphate 5-phosphatase and accumulate phosphatidylinositol 4,5-bisphosphate.''; PubMedEurope PMCScholia
Schmid AC, Wise HM, Mitchell CA, Nussbaum R, Woscholski R.; ''Type II phosphoinositide 5-phosphatases have unique sensitivities towards fatty acid composition and head group phosphorylation.''; PubMedEurope PMCScholia
Wilson MP, Majerus PW.; ''Isolation of inositol 1,3,4-trisphosphate 5/6-kinase, cDNA cloning and expression of the recombinant enzyme.''; PubMedEurope PMCScholia
York JD.; ''Regulation of nuclear processes by inositol polyphosphates.''; PubMedEurope PMCScholia
Nalaskowski MM, Deschermeier C, Fanick W, Mayr GW.; ''The human homologue of yeast ArgRIII protein is an inositol phosphate multikinase with predominantly nuclear localization.''; PubMedEurope PMCScholia
Choi JH, Williams J, Cho J, Falck JR, Shears SB.; ''Purification, sequencing, and molecular identification of a mammalian PP-InsP5 kinase that is activated when cells are exposed to hyperosmotic stress.''; PubMedEurope PMCScholia
Kouchi Z, Shikano T, Nakamura Y, Shirakawa H, Fukami K, Miyazaki S.; ''The role of EF-hand domains and C2 domain in regulation of enzymatic activity of phospholipase Czeta.''; PubMedEurope PMCScholia
Rogers NT, Hobson E, Pickering S, Lai FA, Braude P, Swann K.; ''Phospholipase Czeta causes Ca2+ oscillations and parthenogenetic activation of human oocytes.''; PubMedEurope PMCScholia
Kavanaugh WM, Pot DA, Chin SM, Deuter-Reinhard M, Jefferson AB, Norris FA, Masiarz FR, Cousens LS, Majerus PW, Williams LT.; ''Multiple forms of an inositol polyphosphate 5-phosphatase form signaling complexes with Shc and Grb2.''; PubMedEurope PMCScholia
Ohnishi T, Ohba H, Seo KC, Im J, Sato Y, Iwayama Y, Furuichi T, Chung SK, Yoshikawa T.; ''Spatial expression patterns and biochemical properties distinguish a second myo-inositol monophosphatase IMPA2 from IMPA1.''; PubMedEurope PMCScholia
Cantz M, Gehler J.; ''The mucopolysaccharidoses: inborn errors of glycosaminoglycan catabolism.''; PubMedEurope PMCScholia
Caffrey JJ, Safrany ST, Yang X, Shears SB.; ''Discovery of molecular and catalytic diversity among human diphosphoinositol-polyphosphate phosphohydrolases. An expanding Nudt family.''; PubMedEurope PMCScholia
Brehm MA, Schenk TM, Zhou X, Fanick W, Lin H, Windhorst S, Nalaskowski MM, Kobras M, Shears SB, Mayr GW.; ''Intracellular localization of human Ins(1,3,4,5,6)P5 2-kinase.''; PubMedEurope PMCScholia
In the nucleus, inositol hexakisphosphate kinase 1 (IP6K1) and 2 (IP6K2) phosphorylate inositol 5-diphospho-1,2,3,4,6-pentakisphosphate (5-PP-IP5) to inositol 5-triphospho- 1,2,3,4,6-pentakisphosphate (5-PPP-IP5) (Saiardi et al. 2001, Draskovic et al. 2008) and IP6K2 (Saiardi et al. 2001, Draskovic et al. 2008). While this reaction has been demonstrated to occur in vitro, the extent to which it occurs in vivo is less clear.
Inositol 1,3,4,5,6-pentakisphosphate I(1,3,4,5,6)P5 translocates from the cytosol to the endoplasmic reticulum (ER) lumen (Caffrey et al. 1999, Chi et al. 1999).
Inositol hexakisphosphate kinase 1 (IP6K1) and 3 (IP6K3) phosphorylate inositol 5-diphospho-1,2,3,4,6-pentakisphosphate (5-PP-IP5) to inositol 5-triphospho- 1,2,3,4,6-pentakisphosphate (5-PPP-IP5).
The following lists the above proteins with their corresponding literature references: IP6K1 (Saiardi et al. 2001, Draskovic et al. 2008) and IP6K3 (Saiardi et al. 2001, Draskovic et al. 2008).
Inositol hexakisphosphate kinase 1 (IP6K1) and 3 (IP6K3) phosphorylate inositol 1,2,3,4,5,6-hexakisphosphate (IP6) to inositol 5-diphospho-1,2,3,4,6-pentakisphosphate (5-PP-IP5).
The following lists the above proteins with their corresponding literature references: IP6K1 (Saiardi et al. 2001, Mulugu et al. 2007, Draskovic et al. 2008; Lin et al. 2009) and IP6K3 (Saiardi et al. 2001, Draskovic et al. 2008).
Type II inositol-1,4,5-trisphosphate 5-phosphatase (INPP5B) is attached to the plasma membrane where it dephosphorylates inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) to inositol 1,3,4-trisphosphate (I(1,3,4)P3 (Jefferson & Majerus 1995, Ross et al. 1991, Schmid et al. 2004). INPP5B is isoprenylated at its C-terminus for membrane attachment.
Diphosphoinositol polyphosphate phosphohydrolases, also known as nucleoside diphosphate-linked moiety X motif (NUDT) proteins, dephosphorylate inositol diphospho-pentakisphosphate (PP-IP5) to inositol 1,2,3,4,5,6-hexakisphosphate (IP6). The NUDT proteins involved are: nucleoside diphosphate-linked moiety X motif 3 (NUDT3), 4 (NUDT4), 10 (NUDT10), and 11 (NUDT11). The reactants consumed are: inositol 1-diphospho-2,3,4,5,6-pentakisphosphate (1-PP-IP5) and 3-diphospho-1,2,4,5,6-pentakisphosphate (3-PP-IP5).
The following lists the above proteins with their corresponding literature references: NUDT3 (Safrany et al. 1999, Safrany et al. 1998, Yang et al. 1999, Caffrey et al. 2000), NUDT4 (Caffrey et al. 2000), NUDT10 (Leslie et al. 2002, Hidaka et al. 2002) and NUDT11 (Leslie et al. 2002, Hidaka et al. 2002).
In the nucleus, inositol hexakisphosphate kinase 1 (IP6K1) and 2 (IP6K2) phosphorylate 1-diphospho-2,3,4,5,6-pentakisphosphate (1-PP-IP5) to make inositol 1,5-bisdiphospho-2,3,4,6-tetrakisphosphate (1,5-(PP)2-IP4) (Saiardi et al. 2001, Mulugu et al. 2007).
Inositol monophosphatase 1 (IMPA1) and 2 (IMPA2) homodimers dephosphorylate inositol 4-phosphate (I4P) to inositol (Ins). In vitro, IMPA1 and 2 differ in their pH optima and IMPA1 has a significantly greater activity on IP4 than does IMPA2 (Ohnishi et al. 2007).
Type I (INPP4A) and type II inositol-3,4-bisphosphate 4-phosphatase (INPP4B) dephosphorylate inositol 1,3,4-trisphosphate (I(1,3,4)P3) to inositol 1,3-bisphosphate (I(1,3)P2) (Norris et al. 1995, Norris et al. 1997).
1-diphospho-2,3,4,5,6-pentakisphosphate (1-PP-IP5) and 3-diphospho-1,2,4,5,6-pentakisphosphate (3-PP-IP5) translocate from the cytosol to the nucleus (Saiardi et al. 2001, Mulugu et al. 2007).
Inositol monophosphatase 1 (IMPA1) and 2 (IMPA2) homodimers dephosphorylate inositol 1-phosphate (I1P) to inositol (Ins). In vitro, IMPA1 and 2 differ in their pH optima and IMPA1 has a significantly greater activity on IP4 than does IMPA2 (McAllister et al. 1992, Ohnishi et al. 2007).
A group of inositol phosphatases and the broad specificity enzyme inositol-tetrakisphosphate 1-kinase (ITPK1) dephosphorylate inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) to inositol 1,3,4-trisphosphate (I(1,3,4)P3). The group of inositol phosphatases involved are: inositol polyphosphate 5-phosphatase OCRL-1 (OCRL), phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (INPP5D) aka SHIP1, phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2 (INPPL1) aka SHIP2, phosphatidylinositol 4,5-bisphosphate 5-phosphatase A (INPP5J) aka PIPP, and synaptic inositol-1,4,5-trisphosphate 5-phosphatase 1 (SYNJ1).
The following lists the above proteins with their corresponding literature references: OCRL (Chang et al. 2002, Zhang et al. 1995, Zhang et al. 1998, Schmid et al. 2004); INPP5D (Drayer et al. 1996, Kavanaugh et al. 1996); INPPL1 (Chi et al. 2004); INPP5J (Mochizuki & Thompson 1999); SYNJ1 (Schmid et al. 2004); ITPK1 (Ho et al. 2002).
Inositol monophosphatase 1 (IMPA1) and 2 (IMPA2) homodimers dephosphorylate inositol 3-phosphate (I3P) to inositol (Ins). In vitro, IMPA1 and 2 differ in their pH optima and IMPA1 has a significantly greater activity on IP4 than does IMPA2 (Ohnishi et al. 2007).
Inositol 1,3,4,5,6-pentakisphosphate (I(1,3,4,5,6)P5) translocates from the endoplasmic reticulum (ER) lumen to the nucleus (Verbsky et al. 2002, Brehm et al. 2007, Choi et al. 2007).
Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase aka phosphatase and tensin homolog (PTEN) dephosphorylates inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) to inositol 1,4,5-trisphosphate (I(1,4,5)P3) (Maehama & Dixon 1998, Han et al. 2000).
Inositol 1,4,5-trisphosphate (I(1,4,5)P3) translocates from the endoplasmic reticulum (ER) lumen to the cytosol (Caffrey et al. 1999, Chi et al. 1999).
Inositol-trisphosphate 3-kinase A (ITPKA), B (ITPKB), and C (ITPKC) phosphorylate inositol 1,4,5-trisphosphate (I(1,4,5)P3) to inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) (Dewaste et al. 2003).
Inositol 1,4,5,6-tetrakisphosphate (I(1,4,5,6)P4) translocates from the endoplasmic reticulum (ER) lumen to the nucleus (Caffrey et al. 1999, Chi et al. 1999, Nalaskowski et al. 2002).
Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1/2 (PPIP5K1) and 2 (PPIP5K2) phosphorylate inositol 5-diphospho-1,2,3,4,6-pentakisphosphate (5-PP-IP5) to inositol 1,5-bisdiphospho-2,3,4,6-tetrakisphosphate (1,5-(PP)2-IP4) (Fridy et al. 2007, Mulugu et al. 2007, Choi et al. 2007, Lin et al. 2009).
Diphosphoinositol polyphosphate phosphohydrolase 2, also known as nucleoside diphosphate-linked moiety X motif 4 (NUDT4), dephosphorylates diphospho- tetrakisphosphate (PP-IP4) to inositol 1,3,4,5,6-pentakisphosphate (I(1,3,4,5,6)P5). The products made are: inositol 5-diphospho-1,3,4,6-tetrakisphosphate (5-PP-IP4); inositol 1-diphospho-3,4,5,6-tetrakisphosphate (1-PP-IP4); and inositol 3-diphospho-1,4,5,6-tetrakisphosphate (3-PP-IP4).
The following lists the above protein with its corresponding literature references: NUDT4 (Saiardi et al. 2001, Saiardi et al. 2000).
In the nucleus, inositol hexakisphosphate kinase 1 (IP6K1) and 2 (IP6K2) phosphorylate5-diphospho-1,3,4,6-tetrakisphosphate (5-PP-IP4) to inositol 1,5-bisdiphospho-3,4,6-trisphosphate (1,5-(PP)2-IP3) (Saiardi et al. 2001, Saiardi et al. 2000, Draskovic et al. 2008).
At the endoplasmic reticulum (ER) membrane, phosphoinositide phospholipase C delta-4 (PLCD4) hydrolyses phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) to inositol 1,4,5-trisphosphate (I(1,4,5)P3) and diacylglycerol (DAG). PLCD4 (Leung et al. 2004, Lee et al. 2004) is attached to the ER membrane via its PH domain while its C2 domain binds to the PI(4,5)P2 in the membrane.
Type I (INPP4A) and type II inositol-3,4-bisphosphate 4-phosphatase (INPP4B) dephosphorylate inositol 3,4-bisphosphate (I(3,4)P2) to inositol 3-phosphate (I3P) (Norris et al. 1995, Norris et al. 1997).
At the plasma membrane, a group of phospholipase C (“PLC(bz))” proteins hydrolyse phosphatidylinositol 4,5 bisphosphate (PI(4,5)P2) to inositol 1,4,5 trisphosphate (I(1,4,5)P3) and diacylglycerol (DAG). This group of phospholipase C proteins lack a PH domain and so are is cytosolic. Their C2 domains bind to PI(4,5)P2 at the membrane. The PLC-beta proteins are thought to be responsible for the majority of PI(4,5)P2 hydrolysis.
The phospholipase C isoforms involved and their corresponding literature references are: phosphoinositide phospholipase C beta-1 (PLCB1) (Caricasole et al. 2000, Jhon et al. 1993, Park et al. 1992); beta-2 (PLCB2) (Jhon et al. 1993, Park et al. 1992); beta-3 (PLCB3) (Carozzi et al. 1992, Jhon et al. 1993); beta-4 (PLCB4) (Alvarez et al. 1995, Lee et al. 1993); and zeta-1 (PLCZ1) (Kouchi et al. 2005, Rogers et al. 2004).
In the endoplasmic reticulum (ER) lumen, multiple inositol polyphosphate phosphatase 1 (MINPP1) dephosphorylates inositol 1,3,4,5,6-pentakisphosphate (I(1,3,4,5,6)P5) to inositol 1,4,5,6-tetrakisphosphate (I(1,4,5,6)P4) (Caffrey et al. 1999, Chi et al. 1999).
In the nucleus, inositol hexakisphosphate kinase 1 (IP6K1) and 2 (IP6K2) phosphorylate inositol 1,3,4,5,6-pentakisphosphate (I(1,3,4,5,6)P5) to inositol 5-diphospho-(1,3,4,6)-tetrakisphosphate (5-PP-IP4) (Saiardi et al. 2001, Saiardi et al. 2000, Draskovic et al. 2008).
Inositol 1,3,4,5,6-pentakisphosphate I(1,3,4,5,6)P5 translocates from the nucleus to the cytosol (Nalaskowski et al. 2002; Ho et al. 2002, Brehm et al. 2007).
A group of inositol phosphatases dephosphorylate inositol 1,4,5-trisphosphate (I(1,4,5)P3) to inositol 1,4-bisphosphate (I(1,4)P2). The group of inositol phosphatases involved are: inositol polyphosphate 5-phosphatase OCRL-1 (OCRL), phosphatidylinositol 4,5-bisphosphate 5-phosphatase A (INPP5J), and synaptic inositol-1,4,5-trisphosphate 5-phosphatase 1 (SYNJ1).
The following lists the above proteins with their corresponding literature references: OCRL (Zhang et al. 1995, Zhang et al. 1998, Schmid et al. 2004); INPP5J (Mochizuki & Thompson 1999); SYNJ1 (Schmid et al. 2004).
Inositol hexakisphosphate kinase 1 (IP6K1) and 3 (IP6K3) phosphorylate 1-diphospho-2,3,4,5,6-pentakisphosphate (1-PP-IP5) to form inositol 1,5-bisdiphospho-2,3,4,6-tetrakisphosphate (1,5-(PP)2-IP4) (Saiardi et al. 2001, Mulugu et al. 2007).
In the endoplasmic reticulum (ER) lumen, multiple inositol polyphosphate phosphatase 1 (MINPP1) dephosphorylates inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) to inositol 1,4,5-trisphosphate (I(1,4,5)P3) (Caffrey et al. 1999, Chi et al. 1999).
Inositolpentakisphosphate 2-kinase (IPPK), also known as IP52K, phosphorylates inositol 1,3,4,5,6-pentakisphosphate (I(1,3,4,5,6)P5) to inositol 1,2,3,4,5,6-hexakisphosphate (IP6) (Verbski et al. 2002, Brehm et al. 2007, Choi et al. 2007).
Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1/2 (PPIP5K1) and 2 (PPIP5K2) phosphorylate inositol 1,2,3,4,5,6-hexakisphosphate (IP6) to inositol 1-diphospho-2,3,4,5,6-pentakisphosphate (1-PP-IP5)) (Fridy et al. 2007, Mulugu et al. 2007, Choi et al. 2007, Lin et al. 2009; Wang et al. 2011).
A group of phospholipase C proteins (“PLC(degh)”) bind to the plasma membrane via their PH domains. These phospholipases hydrolyse phosphatidylinositol 4,5 bisphosphate (PI(4,5)P2) to inositol 1,4,5 trisphosphate (I(1,4,5)P3) and diacylglycerol (DAG). The C2 domains of the enzymes bind to PI(4,5)P2 at the membrane.
The phospholipase C isoforms involved and their corresponding literature references are: phosphoinositide phospholipase C delta-1(PLCD1) (Cheng et al. 1995); epsilon-1 (PLCE1) (Song et al. 2001, Lopez et al. 2001); delta-3 (PLCD3) (Pawelczyk & Matecki 1997); gamma-1 (PLCG1) (Harita et al. 2009, Baldassare et al. 1989); gamma-2 (PLCG2) (Banno et al. 1988); eta-1 (PLCH1) (Hwang et al. 2005); and eta-2 (PLCH2) (Zhou et al 2005).
In the endoplasmic reticulum (ER) lumen, multiple inositol polyphosphate phosphatase 1 (MINPP1) dephosphorylates 1,2,3,4,5,6-hexakisphosphate (IP6) to inositol 1,2,4,5,6-pentakisphosphate (I(1,2,4,5,6)P5) (Caffrey et al. 1999, Chi et al. 1999, Deleu et al. 2006, Nogimori et al. 1991).
In the nucleus, inositol-pentakisphosphate 2-kinase (IPPK - also known as IP5-2K) phosphorylates inositol 1,3,4,5,6-pentakisphosphate (I(1,3,4,5,6)P5) to inositol 1,2,3,4,5,6-hexakisphosphate (IP6) (Verbsky et al. 2002, Brehm et al. 2007, Choi et al. 2007).
Inositol 1,3,4,5,6-pentakisphosphate I(1,3,4,5,6)P5 translocates from the endoplasmic reticulum (ER) lumen to the cytosol (Nalaskowski et al. 2002, Ho et al. 2002, Brehm et al. 2007).
Inositol 1,3,4,5-tetrakisphosphate (I(1,3,4,5)P4) translocates from the cytosol to the endoplasmic reticulum (ER) lumen (Caffrey et al. 1999, Chi et al. 1999).
Inositol hexakisphosphate kinase 1 (IP6K1) and 3 (IP6K3) phosphorylate inositol 1-diphospho-3,4,5,6-tetrakisphosphate (1-PP-IP4) to form inositol 1,5-bisdiphospho-3,4,6-trisphosphate (1,5-(PP)2-IP3) (Saiardi et al. 2001, Saiardi et al. 2000, Draskovic et al. 2008).
Inositol 1,5-bisdiphospho-2,3,4,6-tetrakisphosphate (1,5-(PP)2-IP4) and inositol 3,5-bisdiphospho-1,2,4,6-tetrakisphosphate (3,5-(PP)2-IP4) translocate from the nucleus to the cytosol (Leslie et al. 2002).
Type I inositol-1,4,5-trisphosphate 5-phosphatase (INPP5A) and the Type II phosphatase (INPP5B) are isoprenylated to the plasma membrane and act as a lipid anchor. Here they dephosphorylate inositol 1,4,5-trisphosphate (I(1,4,5)P3) to inositol 1,4-bisphosphate I(1,4)P2. ).
The following lists the above proteins with their corresponding literature references: INPP5A (Laxminarayan et al. 1994); INPP5B (Jefferson & Majerus 1995, Ross et al. 1991, Schmid et al. 2004).
In the nucleus, inositol hexakisphosphate kinase 1 (IP6K1) and 2 (IP6K2) phosphorylate inositol 1,2,3,4,5,6-hexakisphosphate (IP6) to inositol 5-diphospho-1,2,3,4,6-pentakisphosphate (5-PP-IP5).
The following lists the above proteins with their corresponding literature references: IP6K1 (Saiardi et al. 2001, Mulugu et al. 2007, Draskovic et al. 2008) and IP6K2 (Saiardi et al. 2001, Mulugu et al. 2007, Draskovic et al. 2008).
Diphosphoinositol polyphosphate phosphohydrolases (DIPP), also known as nucleoside diphosphate-linked moiety X motif (NUDT) proteins, dephosphorylate inositol 5-diphospho-1,2,3,4,6-pentakisphosphate (5-PP-IP5) to inositol 1,2,3,4,5,6-hexakisphosphate (IP6). The NUDT proteins involved are: nucleoside diphosphate-linked moiety X motif 3 (NUDT3), 4 (NUDT4), 10 (NUDT10), and 11 (NUDT11).
The following lists the above proteins with their corresponding literature references: NUDT3 (Safrany et al. 1999, Safrany et al. 1998, Yang et al. 1999, Caffrey et al. 2000), NUDT4 (Caffrey et al. 2000), NUDT10 (Leslie et al. 2002, Hidaka et al. 2002) and NUDT11 (Leslie et al. 2002, Hidaka et al. 2002).
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The following lists the above proteins with their corresponding literature references: IP6K1 (Saiardi et al. 2001, Draskovic et al. 2008) and IP6K3 (Saiardi et al. 2001, Draskovic et al. 2008).
The following lists the above proteins with their corresponding literature references: IP6K1 (Saiardi et al. 2001, Mulugu et al. 2007, Draskovic et al. 2008; Lin et al. 2009) and IP6K3 (Saiardi et al. 2001, Draskovic et al. 2008).
The following lists the above proteins with their corresponding literature references: NUDT3 (Safrany et al. 1999, Safrany et al. 1998, Yang et al. 1999, Caffrey et al. 2000), NUDT4 (Caffrey et al. 2000), NUDT10 (Leslie et al. 2002, Hidaka et al. 2002) and NUDT11 (Leslie et al. 2002, Hidaka et al. 2002).
The following lists the above proteins with their corresponding literature references: OCRL (Chang et al. 2002, Zhang et al. 1995, Zhang et al. 1998, Schmid et al. 2004); INPP5D (Drayer et al. 1996, Kavanaugh et al. 1996); INPPL1 (Chi et al. 2004); INPP5J (Mochizuki & Thompson 1999); SYNJ1 (Schmid et al. 2004); ITPK1 (Ho et al. 2002).
The following lists the above protein with its corresponding literature references: NUDT4 (Saiardi et al. 2001, Saiardi et al. 2000).
The phospholipase C isoforms involved and their corresponding literature references are: phosphoinositide phospholipase C beta-1 (PLCB1) (Caricasole et al. 2000, Jhon et al. 1993, Park et al. 1992); beta-2 (PLCB2) (Jhon et al. 1993, Park et al. 1992); beta-3 (PLCB3) (Carozzi et al. 1992, Jhon et al. 1993); beta-4 (PLCB4) (Alvarez et al. 1995, Lee et al. 1993); and zeta-1 (PLCZ1) (Kouchi et al. 2005, Rogers et al. 2004).
The following lists the above proteins with their corresponding literature references: OCRL (Zhang et al. 1995, Zhang et al. 1998, Schmid et al. 2004); INPP5J (Mochizuki & Thompson 1999); SYNJ1 (Schmid et al. 2004).
The phospholipase C isoforms involved and their corresponding literature references are: phosphoinositide phospholipase C delta-1(PLCD1) (Cheng et al. 1995); epsilon-1 (PLCE1) (Song et al. 2001, Lopez et al. 2001); delta-3 (PLCD3) (Pawelczyk & Matecki 1997); gamma-1 (PLCG1) (Harita et al. 2009, Baldassare et al. 1989); gamma-2 (PLCG2) (Banno et al. 1988); eta-1 (PLCH1) (Hwang et al. 2005); and eta-2 (PLCH2) (Zhou et al 2005).
The following lists the above proteins with their corresponding literature references: INPP5A (Laxminarayan et al. 1994); INPP5B (Jefferson & Majerus 1995, Ross et al. 1991, Schmid et al. 2004).
The following lists the above proteins with their corresponding literature references: IP6K1 (Saiardi et al. 2001, Mulugu et al. 2007, Draskovic et al. 2008) and IP6K2 (Saiardi et al. 2001, Mulugu et al. 2007, Draskovic et al. 2008).
The following lists the above proteins with their corresponding literature references: NUDT3 (Safrany et al. 1999, Safrany et al. 1998, Yang et al. 1999, Caffrey et al. 2000), NUDT4 (Caffrey et al. 2000), NUDT10 (Leslie et al. 2002, Hidaka et al. 2002) and NUDT11 (Leslie et al. 2002, Hidaka et al. 2002).