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Phosphoinositides II: The Diverse Biological Functions pp 389–412Cite as

Defining Signal Transduction by Inositol Phosphates

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Part of the book series: Subcellular Biochemistry ((SCBI,volume 59))

Abstract

Ins(1,4,5)P3 is a classical intracellular messenger: stimulus-dependent changes in its levels elicits biological effects through its release of intracellular Ca2+ stores. The Ins(1,4,5)P3 response is “switched off” by its metabolism to a range of additional inositol phosphates. These metabolites have themselves come to be collectively described as a signaling “family”. The validity of that latter definition is critically examined in this review. That is, we assess the strength of the hypothesis that Ins(1,4,5)P3 metabolites are themselves “classical” signals. Put another way, what is the evidence that the biological function of a particular inositol phosphate depends upon stimulus dependent changes in its levels? In this assessment, examples of an inositol phosphate acting as a cofactor (i.e. its function is not stimulus-dependent) do not satisfy our signaling criteria. We conclude that Ins(3,4,5,6)P4 is, to date, the only Ins(1,4,5)P3 metabolite that has been validated to act as a second messenger.

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References

  • Alcázar-Román AR, Tran EJ, Guo S, Wente SR (2006) Inositol hexakisphosphate and Gle1 activate the DEAD-box protein Dbp5 for nuclear mRNA export. Nat Cell Biol 8:645–647

    Article  CAS  Google Scholar 

  • Ali N, Craxton A, Shears SB (1993) Hepatic Ins(1,3,4,5)P4 3-phosphatase is compartmentalized inside endoplasmic reticulum. J Biol Chem 268:6161–6167

    PubMed  CAS  Google Scholar 

  • Balla T, Guillemette G, Baukal AJ, Catt KJ (1987) Formation of inositol 1,3,4,6-tetrakisphosphate during angiotensin II action in bovine adrenal glomerulosa cells. Biochem Biophys Res Commun 146:199–205

    Article  Google Scholar 

  • Barg S, Huang P, Eliasson L, Nelson DJ, Obermüller S, Rorsman P, Thévenod F, Renström E (2001) Priming of insulin granules for exocytosis by granular chloride uptake and acidification. J Cell Sci 114:2145–2154

    PubMed  CAS  Google Scholar 

  • Barker CJ, Wong NS, Maccallum SM, Hunt PA, Michell RH, Kirk CJ (1992) The interrelationships of the inositol phosphates formed in WRK-1 stimulated rat mammary tumour cells. Biochem J 286:469–474

    PubMed  CAS  Google Scholar 

  • Barker CJ, Leibiger IB, Leibiger B, Berggren PO (2002) Phosphorylated inositol compounds in beta -cell stimulus-response coupling. Am J Physiol Endocrinol Metab 283:E1113–E1122

    PubMed  CAS  Google Scholar 

  • Barker CJ, Wright J, Hughes PJ, Kirk CJ, Michell RH (2004) Complex changes in cellular inositol phosphate complement accompany transit through the cell cycle. Biochem J 380:465–473

    Article  PubMed  CAS  Google Scholar 

  • Batty IH, Downes CP (1994) The inhibition of phosphoinositide synthesis and muscarinic-receptor-mediated phospholipase C activity by Li+ as secondary selective consequences of inositol depletion in 1321N1 cells. Biochem J 297:529–537

    PubMed  CAS  Google Scholar 

  • Batty IH, Nahorski SR, Irvine RF (1985) Rapid formation of inositol 1,3,4-tetrakisphosphate following muscarinic receptor stimulation of rat cerebral cortical slices. Biochem J 232:211–215

    PubMed  CAS  Google Scholar 

  • Batty IH, Currie RA, Downes CP (1998) Evidence for a model of integrated inositol phospholipid pools implies an essential role for lipid transport in the maintenance of receptor-mediated phospholipase C activity in 1321N1 cells. Biochem J 330:1069–1077

    PubMed  CAS  Google Scholar 

  • Becker PB, Hörz W (2002) ATP-dependent nucleosome remodeling. Annu Rev Biochem 71:247–273

    Article  PubMed  CAS  Google Scholar 

  • Berggren PO, Barker CJ (2008) A key role for phosphorylated inositol compounds in pancreatic beta-cell stimulus-secretion coupling. Adv Enzyme Regul 48:276–294

    Article  PubMed  CAS  Google Scholar 

  • Bird GStJ, Putney JW Jr (1996) Effect of inositol 1,3,4,5-tetrakisphosphate on inositol trisphosphate-activated Ca2+ signaling in mouse lacrimal acinar cells. J Biol Chem 271:6766–6770

    Article  PubMed  CAS  Google Scholar 

  • Bird GStJ, Rossier MF, Hughes AR, Shears SB, Armstrong DL, Putney JW Jr (1991) Activation of calcium entry into acinar cells by a non-phosphorylatable inositol trisphosphate. Nature 352:162–165

    Article  PubMed  CAS  Google Scholar 

  • Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39

    Article  PubMed  CAS  Google Scholar 

  • Boynton AL, Dean NM, Hill TD (1990) Inositol 1,3,4,5-tetrakisphosphate and regulation of intracellular calcium. Biochem Pharmacol 40:1933–1939

    Article  PubMed  CAS  Google Scholar 

  • Brehm MA, Schenk TM, Zhou X, Fanick W, Lin H, Windhorst S, Nalaskowski MM, Kobras M, Shears SB, Mayr GW (2007) Intracellular localization of human inositol 1,3,4,5,6-pentakisphosphate 2-kinase. Biochem J 408:335–345

    Article  PubMed  CAS  Google Scholar 

  • Brough D, Bhatti F, Irvine RF (2005) Mobility of proteins associated with the plasma membrane by interaction with inositol lipids. J Cell Sci 118:3019–3025

    Article  PubMed  CAS  Google Scholar 

  • Bunce CM, French PJ, Allen P, Mountford JC, Moor B, Greaves MF, Michell RH, Brown G (1993) Comparison of the levels of inositol metabolites in transformed haemopoietic cells and their normal counterparts. Biochem J 289:667–673

    PubMed  CAS  Google Scholar 

  • Caffrey JJ, Darden T, Wenk MR, Shears SB (2001) Expanding Coincident Signaling by PTEN through its Inositol 1,3,4,5,6-Pentakisphosphate 3-phosphatase Activity. FEBS Lett 499:6–10

    Article  PubMed  CAS  Google Scholar 

  • Carew MA, Yang X, Schultz C, Shears SB (2000) Ins(3,4,5,6)P4 inhibits an apical calcium-activated chloride conductance in polarized monolayers of a cystic fibrosis cell-line. J Biol Chem 275:26906–26913

    PubMed  CAS  Google Scholar 

  • Chamberlain PP, Qian X, Stiles AR, Cho J, Jones DH, Lesley SA, Grabau EA, Shears SB, Spraggon G (2007) Integration of inositol phosphate signaling pathways via human ITPK1. J Biol Chem 282:28117–28125

    Article  PubMed  CAS  Google Scholar 

  • Changya L, Gallacher DV, Irvine RF, Potter BVL, Petersen OH (1989) Inositol 1,3,4,5-trisphosphate is essential for sustained activation of the Ca2+-dependent K+ current in single internally perfused lacrimal cells. J Membr Biol 109:85–93

    Article  PubMed  CAS  Google Scholar 

  • Cheung JC, Salerno B, Hanakahi LA (2008) Evidence for an inositol hexakisphosphate-dependent role for Ku in mammalian nonhomologous end joining that is independent of its role in the DNA-dependent protein kinase. Nucleic Acids Res 36:5713–5726

    Article  PubMed  CAS  Google Scholar 

  • Chi H, Yang X, Kingsley PD, O’Keefe RJ, Puzas JE, Rosier RN, Shears SB, Reynolds PR (2000) Targeted deletion of Minpp1 provides new insight into the activity of multiple inositol polyphosphate phosphatase in vivo. Mol Cell Biol 20:6496–6507

    Article  PubMed  CAS  Google Scholar 

  • Claud EC, Lu J, Wang XQ, Abe M, Petrof EO, Sun J, Nelson DJ, Marks JD, Jilling T (2008) Platelet-activating Factor induced chloride channel activation is associated with intracellular acidosis and apoptosis of intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 294, G1191-G1200

    Article  PubMed  CAS  Google Scholar 

  • Cooke F, Poyner DR, Hawkins P, Erlebach C, Hanley MR (1991) Inositol hexakisphosphate-membranes interactions: the role of metal ions. Biochem Soc Trans 19:152s

    Google Scholar 

  • Cozier GE, Lockyer PJ, Reynolds JS, Kupzig S, Bottomley JR, Millard TH, Banting G, Cullen PJ (2000) GAP1IP4BP contains a novel group I pleckstrin homology domain that directs constitutive plasma membrane association. J Biol Chem 275:28261–28628

    PubMed  CAS  Google Scholar 

  • Craxton A, Caffrey JJ, Burkhart W, Safrany ST, Shears SB (1997) Cloning and expression of rat hepatic multiple inositol polyphosphate phosphatase. Biochem J 328:75–81

    PubMed  CAS  Google Scholar 

  • Crossley I, Swann K, Chambers E, Whitaker M (1988) Activation of sea urchin eggs by inositol phosphates is independent of external calcium. Biochem J 252:257–262

    PubMed  CAS  Google Scholar 

  • Cuddapah VA, Sontheimer H (2010) Molecular interaction and functional regulation of ClC-3 by Ca2+/calmodulin-dependent protein kinase II (CaMKII) in human malignant glioma. J Biol Chem 285:11188–11196

    Article  PubMed  CAS  Google Scholar 

  • Cullen PJ, Hsuan JJ, Truong O, Letcher AJ, Jackson TR, Dawson AP, Irvine RF (1995) Identification of a specific Ins(1,3,4,5)P4-binding protein as a member of the GAP1 family. Nature 376:527–530

    Article  PubMed  CAS  Google Scholar 

  • Dubois E, Dewaste V, Erneux C, Messenguy F (2000) Inositol polyphosphate kinase activity of Arg82/ArgRIII is not required for the regulation of the arginine metabolism in yeast. FEBS Lett 486:300–304

    Article  PubMed  CAS  Google Scholar 

  • Eckmann L, Rudolf MT, Ptasznik A, Schultz C, Jiang T, Wolfson N, Tsien R, Fierer J, Shears SB, Kagnoff MF, Traynor-Kaplan A (1997) D-myo-inositol 1,4,5,6-tetrakisphosphate produced in human intestinal epithelial cells in response to Salmonella invasion inhibits phosphoinositide 3-kinase signaling pathways. Proc Natl Acad Sci U S A 94:14456–14460

    Article  PubMed  CAS  Google Scholar 

  • El Alami M, Messenguy F, Scherens B, Dubois E (2003) Arg82p is a bifunctional protein whose inositol polyphosphate kinase activity is essential for nitrogen and PHO gene expression but not for Mcm1p chaperoning in yeast. Mol Microbiol 49:457–468

    Google Scholar 

  • Frederick JP, Mattiske D, Wofford JA, Megosh LC, Drake LY, Chiou ST, Hogan BL, York JD (2005) An essential role for an inositol polyphosphate multikinase, Ipk2, in mouse embryogenesis and second messenger production. Proc Natl Acad Sci U S A 102:8454–8459

    Article  PubMed  CAS  Google Scholar 

  • Gao Y, Wang HY (2007) Inositol Pentakisphosphate Mediates Wnt/beta-Catenin Signaling. J Biol Chem 282:26490–26502

    Article  PubMed  CAS  Google Scholar 

  • Gentzsch M, Cui L, Mengos A, Chang XB, Chen JH, Riordan JR (2003) The PDZ-binding chloride channel ClC-3B localizes to the Golgi and associates with cystic fibrosis transmembrane conductance regulator-interacting PDZ proteins. J Biol Chem 278:6440–6449

    Article  PubMed  CAS  Google Scholar 

  • Guse AH, Greiner E, Emmrich F, Brand K (1993) Mass changes of inositol 1,3,4,5,6-pentakisphosphate and inositol hexakisphosphate during cell cycle progression in rat thymocytes. J Biol Chem 268:7129–7133

    PubMed  CAS  Google Scholar 

  • Hara-Chikuma M, Yang B, Sonawane ND, Sasaki S, Uchida S, Verkman AS (2005) ClC-3 chloride channels facilitate endosomal acidification and chloride accumulation. J Biol Chem 280:1241–1247

    Article  PubMed  CAS  Google Scholar 

  • Hermosura MC, Takeuchi H, Fleig A, Riley AQM, Potter BVL, Hirata M, Penner R (2000) InsP4 facilitates store-operated calcium influx by inhibition of InsP3 5-phosphatase. Nature 408:735–740

    Article  PubMed  CAS  Google Scholar 

  • Hernandez LD, Hueffer K, Wenk MR, Galan JE (2004) Salmonella modulates vesicular traffic by altering phosphoinositide metabolism. Science 304:1805–1807

    Article  PubMed  CAS  Google Scholar 

  • Heslop JP, Irvine RF, Tashjian AH, Berridge MJ (1985) Inositol tetrakis- and pentakisphosphates in GH4 cells. J Exp Biol 119:395–401

    PubMed  CAS  Google Scholar 

  • Hill TD, Dean NM, Boynton AL (1988) Inositol 1,3,4,5-tetrakisphosphate induces Ca2+ sequestration in rat liver cells. Science 242:1176–1178

    Article  PubMed  CAS  Google Scholar 

  • Ho MWY, Shears SB (2002) Regulation of calcium-activated chloride channels by inositol 3,4,5,6-tetrakisphosphate. In: Fuller CM (ed) Current topics in membranes, 53. Academic Press, London, pp 345–363

    Google Scholar 

  • Ho MWY, Carew MA, Yang X, Shears SB (2000) Regulation of chloride channel conductance by Ins(3,4,5,6)P4; a phosphoinositide-initiated signalling pathway that acts downstream of Ins(1,4,5)P3. In: Cockroft S (ed) Frontiers in molecular biology: biology of phosphoinositides. Oxford University Press, Oxford, pp 298–319

    Google Scholar 

  • Ho MWY, Kaetzel MA, Armstrong DL, Shears SB (2001) Regulation of a human chloride channel: a paradigm for integrating input from calcium, CaMKII and Ins(3,4,5,6)P4. J Biol Chem 276:18673–18680

    Article  PubMed  CAS  Google Scholar 

  • Ho MWY, Yang X, Carew MA, Zhang T, Hua L, Kwon Y-U, Chung S-K, Adelt S, Vogel G, Riley AM, Potter BVL, Shears SB (2002) Regulation of Ins(3456)P4 signaling by a reversible kinase/phosphatase. Curr Biol 12:477–482

    Article  PubMed  CAS  Google Scholar 

  • Hoth M, Penner R (1992) Depletion of intracellular calcium stores activates a calcium current in mast cells. Nature 355:353–356

    Article  PubMed  CAS  Google Scholar 

  • Huang YH, Grasis JA, Miller AT, Xu R, Soonthornvacharin S, Andreotti AH, Tsoukas CD, Cooke MP, Sauer K (2007) Positive regulation of Itk PH domain function by soluble IP4. Science 316:886–889

    Article  PubMed  CAS  Google Scholar 

  • Irvine RF (1986) Calcium transients: mobilization of intracellular Ca2+. Br Med Bull 42:369–374

    PubMed  CAS  Google Scholar 

  • Irvine RF (1992) Is inositol tetrakisphosphate the second messenger that controls Ca2+ entry into cells? In: Putney JW Jr (ed) Advances in second messenger and phosphoprotein research. Raven Press, New York, pp 161–185

    Google Scholar 

  • Irvine RF, Moor RM (1986) Micro-injection of inositol 1,3,4,5-tetrakisphosphate activates sea urchin eggs by a mechanism dependent on external Ca2+. Biochem J 240:917–920

    PubMed  CAS  Google Scholar 

  • Irvine RF, Moor RM (1987) Inositol(1,3,4,5)tetrakisphosphate-induced activation of sea urchin eggs requires the presence of inositol trisphosphate. Biochem Biophys Res Commun 146:284–290

    Article  PubMed  CAS  Google Scholar 

  • Irvine RF, Schell M (2001) Back in the water: the return of the inositol phosphates. Nat Rev Mol Cell Biol 2:327–338

    Article  PubMed  CAS  Google Scholar 

  • Irvine RF, Letcher AJ, Heslop JP, Berridge MJ (1986) The inositol tris/tetrakisphosphate pathway—demonstration of Ins(1,4,5)P3 3-kinase activity in animal tissues. Nature 320:631–634

    Article  PubMed  CAS  Google Scholar 

  • Irvine RF, Lloyd-Burton SM, Yu JC, Letcher AJ, Schell MJ (2006) The regulation and function of inositol 1,4,5-trisphosphate 3-kinases. Adv Enzyme Regul 46:314–323

    Article  PubMed  CAS  Google Scholar 

  • Ismailov II, Fuller CM, Berdiev BK, Shlyonsky VG, Benos DJ, Barrett KE (1996) A biologic function for an “orphan” messenger: D-myo-Inositol 3,4,5,6-tetrakisphosphate selectively blocks epithelial calcium-activated chloride current. Proc Nat Acad Sci U S A 93:10505–10509

    Article  CAS  Google Scholar 

  • Jentsch TJ (2008) CLC chloride channels and transporters: from genes to protein structure, pathology and physiology. Crit Rev Biochem Mol Biol 43:3–36

    Article  PubMed  CAS  Google Scholar 

  • Jentsch TJ, Stein V, Weinreich F, Zdebik AA (2002) Molecular structure and physiological function of chloride channels. Physiol Rev 82:503–568

    PubMed  CAS  Google Scholar 

  • Jia Y, Subramanian KK, Erneux C, Pouillon V, Hattori H, Jo H, You J, Zhu D, Schurmans S, Luo HR (2007) Inositol 1,3,4,5-tetrakisphosphate negatively regulates phosphatidylinositol-3,4,5- trisphosphate signaling in neutrophils. Immunity 27:453–467

    Article  PubMed  CAS  Google Scholar 

  • Jia Y, Loison F, Hattori H, Li Y, Erneux C, Park SY, Gao C, Chai L, Silberstein LE, Schurmans S, Luo HR (2008) Inositol trisphosphate 3-kinase B (InsP3KB) as a physiological modulator of myelopoiesis. Proc Natl Acad Sci U S A 105:4739–4744

    Article  PubMed  CAS  Google Scholar 

  • Kavran JM, Klein DE, Lee A, Falasca M, Isakoff SJ, Skolnik EY, Lemmon MA (1998) Specificity and Promiscuity in phosphoinositide binding by pleckstrin homology domains. J Biol Chem 273:30497–30508

    Article  PubMed  CAS  Google Scholar 

  • Komander D, Fairservice A, Deak M, Kular GS, Prescott AR, Peter DC, Safrany ST, Alessi DR, Aalten DM van (2004) Structural insights into the regulation of PDK1 by phosphoinositides and inositol phosphates. EMBO J 23:3918–3928

    Article  PubMed  CAS  Google Scholar 

  • Larsson O, Barker CJ, Sj-oholm A, Carlqvist H, Michell RH, Bertorello A, Nilsson T, Honkanen RE, Mayr GW, Zwiller J, Berggren PO (1997) Inhibition of phosphatases and increased Ca2+ channel activity by inositol hexakisphosphate. Science 278:471–474

    Article  PubMed  CAS  Google Scholar 

  • Leyman A, Pouillon V, Bostan A, Schurmans S, Erneux C, Pesesse X (2007) The absence of expression of the three isoenzymes of the inositol 1,4,5-trisphosphate 3-kinase does not prevent the formation of inositol pentakisphosphate and hexakisphosphate in mouse embryonic fibroblasts. Cell Signal 19:1497–1504

    Article  PubMed  CAS  Google Scholar 

  • Li W, Schultz C, Llopis J, Tsien RY (1997) Membrane-permeant esters of inositol polyphosphates, chemical synthesis and biological applications. Tetrahedron 53:12017–12040

    Article  CAS  Google Scholar 

  • Loomis-Husselbee JW, Cullen PJ, Dreikausen UE, Irvine RF, Dawson AP (1996) Synergistic effects of inositol 1,3,4,5-tetrakisphosphate on inositol 2,4,5-trisphosphate-stimulated Ca2+ release do not involve direct interaction of inositol 1,3,4,5-tetrakisphosphate with inositol trisphosphate binding sites. Biochem J 314:811–816

    PubMed  CAS  Google Scholar 

  • Luckhoff A, Clapham DE (1992) Inositol 1,3,4,5-tetrakisphosphate activates an endothelial Ca2+-permeable channel. Nature 355:356–358

    Article  PubMed  CAS  Google Scholar 

  • Macbeth MR, Schubert HL, Vandemark AP, Lingam AT, Hill CP, Bass BL (2005) Inositol hexakisphosphate is bound in the ADAR2 core and required for RNA editing. Science 309:1534–1539

    Article  PubMed  CAS  Google Scholar 

  • Mao J, Chen L, Xu B, Wang L, Li H, Guo J, Li W, Nie S, Jacob TJ, Wang L (2008) Suppression of ClC-3 channel expression reduces migration of nasopharyngeal carcinoma cells. Biochem Pharmacol 75:1706–1716

    Article  PubMed  CAS  Google Scholar 

  • Marechal Y, Pesesse X, Jia Y, Pouillon V, Perez-Morga D, Daniel J, Izui S, Cullen PJ, Leo O, Luo HR, Erneux C, Schurmans S (2007) Inositol 1,3,4,5-tetrakisphosphate controls proapoptotic Bim gene expression and survival in B cells. Proc Natl Acad Sci U S A 104:13978–13983

    Article  PubMed  CAS  Google Scholar 

  • Mattingly RR, Stephens LR, Irvine RF, Garrison JC (1991) Effects of transformation with the v-src oncogene on inositol phosphate metabolism in rat-1 fibroblasts: D-myo-inositol 1,4,5,6-tetrakisphosphate is increased in v-src transformed rat-1 fibroblasts and can be synthesised from d-myo-inositol 1,3,4-trisphosphate in cytosolic extracts. J Biol Chem 266:15144–15153

    PubMed  CAS  Google Scholar 

  • McKnight S (2003) Gene switching by metabolic enzymes—how did you get on the invitation list? Cell 174:150–152

    Article  Google Scholar 

  • Menniti FS, Oliver KG, Nogimori K, Obie JF, Shears SB, Putney JW Jr (1990) Origins of myo-inositol tetrakisphosphates in agonist-stimulated rat pancreatoma cells. Stimulation by bombesin of myo-inositol 1,3,4,5,6-pentakisphosphate breakdown to myo-inositol 3,4,5,6-tetrakisphosphate. J Biol Chem 265:11167–11176

    PubMed  CAS  Google Scholar 

  • Menniti FS, Miller RN, Putney JW Jr, Shears SB (1993) Turnover of inositol polyphosphate pyrophosphates in pancreatoma cells. J Biol Chem 268:3850–3856

    PubMed  CAS  Google Scholar 

  • Michell RH, King CE, Piper CJ, Stephens LR, Bunce CM, Guy GR, Brown G (1988) Inositol lipids and phosphates in erythrocytes and HL60 cells. J Gen Physiol 43:345–355

    CAS  Google Scholar 

  • Miller GJ, Wilson MP, Majerus PW, Hurley JH (2005) Specificity determinants in inositol polyphosphate synthesis: crystal structure of inositol 1,3,4-trisphosphate 5/6-kinase. Mol Cell 18:201–212

    Article  PubMed  CAS  Google Scholar 

  • Miller AT, Sandberg M, Huang YH, Young M, Sutton S, Sauer K, Cooke MP (2007) Production of Ins(1,3,4,5)P4 mediated by the kinase Itpkb inhibits store-operated calcium channels and regulates B cell selection and activation. Nat Immunol 8:514–521

    Article  PubMed  CAS  Google Scholar 

  • Miller AT, Beisner DR, Liu D, Cooke MP (2009) Inositol 1,4,5-trisphosphate 3-kinase B is a negative regulator of BCR signaling that controls B cell selection and tolerance induction. J Immunol 182:4696–4704

    Article  PubMed  CAS  Google Scholar 

  • Mitchell J, Wang X, Zhang G, Gentzsch M, Nelson DJ, Shears SB (2008) An Expanded Biological Repertoire for Ins(3,4,5,6)P(4) through its Modulation of ClC-3 Function. Curr Biol 18:1600–1605

    Article  PubMed  CAS  Google Scholar 

  • Monserrate JP, York JD (2010) Inositol phosphate synthesis and the nuclear processes they affect. Curr Opin Cell Biol 22:365–373

    Article  PubMed  CAS  Google Scholar 

  • Morris AP, Gallacher DV, Irvine RF, Petersen OH (1987) Synergism of inositol trisphosphate and tetrakisphosphate in activating Ca2+-dependent K+ channels. Nature 330:653–655

    Article  PubMed  CAS  Google Scholar 

  • Nagy R, Grob H, Weder B, Green P, Klein M, Frelet A, Schjoerring JK, Brearley CA, Martinoia E (2009) The Arabidopsis ATP-binding cassette protein ATMRP5/ATABCC5 is a high-affinity inositol hexakisphosphate transporter involved in guard cell signaling and phytate storage. J Biol Chem 284:33614–33622

    Google Scholar 

  • Nalaskowski MM, Deschermeier C, Fanick W, Mayr GW (2002) The human homologue of yeast ArgRIII protein is an inositol phosphate multikinase with predominantly nuclear localization. Biochem J 366:549–556

    Article  PubMed  CAS  Google Scholar 

  • Narayan K, Lemmon MA (2006) Determining selectivity of phosphoinositide-binding domains. Methods 39:122–133

    Article  PubMed  CAS  Google Scholar 

  • Nishi T, Forgac M (2002) The vacuolar (H+)-ATPases—nature’s most versatile proton pumps. Nat Rev Mol Cell Biol 3:94–103

    Article  PubMed  CAS  Google Scholar 

  • Norris FA, Wilson MP, Wallis TS, Galyov EE, Majerus PW (1998) SopB, a protein required for virulence of Salmonella dublin, is an inositol phosphate phosphatase. Proc Natl Acad Sci U S A 95:14057–14059

    Article  PubMed  CAS  Google Scholar 

  • Odom AR, Stahlberg A, Wente SR, York JD (2000) A role for nuclear inositol 1,4,5-trisphosphate kinase in transcriptional control. Science 287:2026–2029

    Article  PubMed  CAS  Google Scholar 

  • Oliver KG, Putney JW Jr, Obie JF, Shears SB (1992) The interconversion of inositol 1,3,4,5,6-pentakisphosphate and inositol tetrakisphosphates in AR4–2J cells. J Biol Chem 267:21528–21534

    PubMed  CAS  Google Scholar 

  • Otto JC, Kelly P, Chiou ST, York JD (2007) Alterations in an inositol phosphate code through synergistic activation of a G protein and inositol phosphate kinases. Proc Natl Acad Sci U S A 104:15653–15658

    Article  PubMed  CAS  Google Scholar 

  • Parekh AB, Penner R (1997) Store depletion and calcium influx. Physiol Rev 77:901–930

    PubMed  CAS  Google Scholar 

  • Pittet D, Schlegel W, Lew DP, Monod A, Mayr GW (1989) Mass changes in inositol tetrakis- and pentakisphosphate isomers induced by chemotactic peptide stimulation in HL-60 cells. J Biol Chem 264:18489–18493

    PubMed  CAS  Google Scholar 

  • Pouillon V, Hascakova-Bartova R, Pajak B, Adam E, Bex F, Dewaste V, Van Lint C, Leo O, Erneux C, Schurmans S (2003) Inositol 1,3,4,5-tetrakisphophate is essential for T lymphocyte development. Nat Immunol 4:1136–1143

    Article  PubMed  CAS  Google Scholar 

  • Putney JW Jr (1986) A model for receptor-regulated calcium entry. Cell Calcium 7:1–12

    Article  PubMed  CAS  Google Scholar 

  • Putney JW Jr (1992) Inositol phosphates and calcium entry. In: Putney JW (ed) Advances in second messenger and phosphoprotein research. Raven Press, New York, pp 143–160

    Google Scholar 

  • Qi Q, August A (2009) The Tec family kinase Itk exists as a folded monomer in vivo. J Biol Chem 284:29882–29892

    Article  PubMed  CAS  Google Scholar 

  • Qi Q, Sahu N, August A (2006) Tec kinase Itk forms membrane clusters specifically in the vicinity of recruiting receptors. J Biol Chem 281:38529–38534

    Article  PubMed  CAS  Google Scholar 

  • Quignard JF, Rakotoarisoa L, Mironneau J, Mironneau C (2003) Stimulation of L-type Ca2+ channels by inositol pentakis- and hexakisphosphates in rat vascular smooth muscle cells. J Physiol 549:729–737

    Article  PubMed  CAS  Google Scholar 

  • Rall TW, Sutherland EW (1958) Formation of a cyclic adenine ribonucleotide by tissue particles. J Biol Chem 232:1065–1076

    PubMed  CAS  Google Scholar 

  • Renström E, Ivarsson R, Shears SB (2002) Ins(3,4,5,6)P4 inhibits insulin granule acidification and fusogenic potential. J Biol Chem 277:26717–26720

    Article  PubMed  CAS  Google Scholar 

  • Robison GA, Butcher RW, Sutherland EW (1968) Cyclic AMP. Annu Rev Biochem 37:149–174

    Article  PubMed  CAS  Google Scholar 

  • Ruzzene M, Pinna LA (2010) Addiction to protein kinase CK2: a common denominator of diverse cancer cells? Biochim Biophys Acta 1804:499–504

    Article  PubMed  CAS  Google Scholar 

  • Saiardi A (2011) Phosphoinositides and inositol phosphates

    Google Scholar 

  • Saiardi A, Caffrey JJ, Snyder SH, Shears SB (2000) Inositol polyphosphate multikinase (ArgRIII) determines nuclear mRNA export in Saccharomyces cerevisiae. FEBS Lett 468:28–32

    Article  PubMed  CAS  Google Scholar 

  • Saiardi A, Nagata E, Luo HR, Sawa A, Luo X, Snowman AM, Snyder SH (2001) Mammalian inositol polyphosphate multikinase synthesizes inositol 1,4,5-trisphosphate and an inositol pyrophosphate. Proc Natl Acad Sci U S A 98:2306–2311

    Article  PubMed  CAS  Google Scholar 

  • Sakaguchi R, Tainaka K, Shimada N, Nakano S, Inoue M, Kiyonaka S, Mori Y, Morii T (2010) An in vivo fluorescent sensor reveals intracellular ins(1,3,4,5)P4 dynamics in single cells. Angew Chem Int Ed Engl 49:2150–2153

    Article  PubMed  CAS  Google Scholar 

  • Sarmah B, Wente SR (2010) Inositol hexakisphosphate kinase-2 acts as an effector of the vertebrate Hedgehog pathway. Proc Natl Acad Sci U S A 107:19921–19926

    Article  PubMed  CAS  Google Scholar 

  • Sarmah B, Latimer AJ, Appel B, Wente SR (2005) Inositol polyphosphates regulate zebrafish left-right asymmetry. Dev Cell 9:133–145

    Article  PubMed  CAS  Google Scholar 

  • Sauer K, Cooke MP (2010) Regulation of immune cell development through soluble inositol-1,3,4,5-tetrakisphosphate. Nat Rev Immunol 10:257–271

    Article  PubMed  CAS  Google Scholar 

  • Schell MJ (2010) Inositol trisphosphate 3-kinases: focus on immune and neuronal signaling. Cell Mol Life Sci 67:1755–1778

    Google Scholar 

  • Schell MJ, Irvine RF (2006) Calcium-triggered exit of F-actin and IP(3) 3-kinase A from dendritic spines is rapid and reversible. Eur J Neurosci 24:2491–2503

    Article  PubMed  Google Scholar 

  • Seeds AM, Sandquist JC, Spana EP, York JD (2004) A molecular basis for inositol polyphosphate synthesis in Drosophila melanogaster. J Biol Chem 279:47222–47232

    Google Scholar 

  • Shears SB (1989) Metabolism of the inositol phosphates produced by receptor activation. Biochem J 260:313–324

    PubMed  CAS  Google Scholar 

  • Shears SB (2004) How versatile are inositol phosphate kinases? Biochem J 377:265–280

    Article  PubMed  CAS  Google Scholar 

  • Shears SB, Parry JB, Tang EKY, Irvine RF, Michell RH, Kirk CJ (1987) Metabolism of D-myo-inositol 1,3,4,5-tetrakisphosphate by rat liver, including the synthesis of a novel isomer of myo-inositol tetrakisphosphate. Biochem J 246:139–147

    PubMed  CAS  Google Scholar 

  • Shen X, Xiao H, Ranallo R, Wu W-H, Wu C (2003) Modulation of ATP-dependent chromatin-remodeling complexes by inositol polyphosphates. Science 299:112–114

    Article  PubMed  CAS  Google Scholar 

  • Shi J, Wang H, Schellin K, Li B, Faller M, Stoop JM, Meeley RB, Ertl DS, Ranch JP, Glassman K (2007) Embryo-specific silencing of a transporter reduces phytic acid content of maize and soybean seeds. Nat Biotechnol 25:930–937

    Article  PubMed  CAS  Google Scholar 

  • Slusarski DC, Corces VG, Moon RT (1997) Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling. Nature 390:410–413

    Article  PubMed  CAS  Google Scholar 

  • Smith PM, Harmer AR, Letcher AJ, Irvine RF (2000) The effect of inositol 1,3,4,5-tetrakisphosphate on inositol trisphosphate-induced Ca2+ mobilization in freshly isolated and cultured mouse lacrimal cells. Biochem J 347:77–82

    Article  PubMed  CAS  Google Scholar 

  • Solyakov L, Cain K, Tracey BM, Jukes R, Riley AM, Potter BV, Tobin AB (2004) Regulation of casein kinase-2 (CK2) activity by inositol phosphates. J Biol Chem279:43403–43410

    Google Scholar 

  • Steger DJ, Haswell ES, Miller AL, Wente SR, O’Shea EK (2003) Regulation of chromatin remodeling by inositol polyphosphates. Science 299:114–116

    Article  PubMed  CAS  Google Scholar 

  • Stobrawa SM, Breiderhoff T, Takamori S, Engel D, Schweizer M, Zdebik AA, Bösl MR, Ruether K, Jahn H, Draguhn A, Jahn R, Jentsch TJ (2001) Disruption of ClC-3, a chloride channel expressed on synaptic vesicles, leads to a loss of hippocampus. Neuron 29:185–196

    Article  PubMed  CAS  Google Scholar 

  • Streb H, Irvine RF, Berridge MJ, Schulz I (1983) Release of Ca2+ from a nonmitochondrial store in pancreatic cells by inositol-1,4,5-trisphosphate. Nature 306:67–68

    Article  PubMed  CAS  Google Scholar 

  • Stuart JA, Anderson KL, French PJ, Kirk CJ, Michell RH (1994) The intracellular distribution of inositol polyphosphates in HL60 promyeloid cells. Biochem J 303:517–525

    PubMed  CAS  Google Scholar 

  • Sutherland EW, Rall TW (1958) Fractionation and characterization of a cyclic adenine ribonucleotide formed by tissue particles. J Biol Chem 232:1077–1091

    PubMed  CAS  Google Scholar 

  • Taylor C (2011) Phosphoinositides and inositol phosphates

    Google Scholar 

  • Vajanaphanich M, Schultz C, Rudolf MT, Wasserman M, Enyedi P, Craxton A, Shears SB, Tsien RY, Barrett KE, Traynor-Kaplan AE (1994) Long-term uncoupling of chloride secretion from intracellular calcium levels by Ins(3,4,5,6)P4. Nature 371:711–714

    Article  PubMed  CAS  Google Scholar 

  • Vallejo M, Jackson T, Lightman S, Hanley MR (1987) Occurrence and extracellular actions of inositol pentakis- and hexakisphosphate in mammalian brain. Nature 330:656–658

    Article  PubMed  CAS  Google Scholar 

  • Verbsky J, Lavine K, Majerus PW (2005a) Disruption of the mouse inositol 1,3,4,5,6-pentakisphosphate 2-kinase gene, associated lethality, and tissue distribution of 2-kinase expression. Proc Natl Acad Sci U S A 102:8448–8453

    Article  CAS  Google Scholar 

  • Verbsky JW, Chang SC, Wilson MP, Mochizuki Y, Majerus PW (2005b) The pathway for the production of inositol hexakisphosphate in human cells. J Biol Chem 280:1911–1920

    Article  CAS  Google Scholar 

  • Volk AP, Heise CK, Hougen JL, Artman CM, Volk KA, Wessels D, Soll DR, Nauseef WM, Lamb FS, Moreland JG (2008) ClC-3 and IClswell are required for normal neutrophil chemotaxis and shape change. J Biol Chem 283:34315–34326

    Article  PubMed  CAS  Google Scholar 

  • von Zastrow M, Sorkin A (2007) Signaling on the endocytic pathway. Curr Opin Cell Biol 19:436–445

    Article  PubMed  CAS  Google Scholar 

  • Walker SA, Kupzig S, Lockyer PJ, Bilu S, Zharhary D, Cullen PJ (2002) Analysing the role of the putative inositol 1,3,4,5-tetrakisphosphate receptor GAP1IP4BP in intracellular Ca2+ homeostasis. J Biol Chem 277:48779–48785

    Article  PubMed  CAS  Google Scholar 

  • Wang XQ, Deriy LV, Foss S, Huang P, Lamb FS, Kaetzel MA, Bindokas V, Marks JD, Nelson DJ (2006) CLC-3 channels modulate excitatory synaptic transmission in hippocampal neurons. Neuron 52:321–333

    Article  PubMed  CAS  Google Scholar 

  • Wilson MP, Hugge C, Bielinska M, Nicholas P, Majerus PW, Wilson DB (2009) Neural tube defects in mice with reduced levels of inositol 1,3,4-trisphosphate 5/6-kinase. Proc Natl Acad Sci U S A 106:9831–9835

    Google Scholar 

  • Xie W, Kaetzel MA, Bruzik KS, Dedman JR, Shears SB, Nelson DJ (1996) Inositol 3,4,5,6-tetrakisphosphate inhibits the calmodulin-dependent protein kinase II-activated chloride conductance inT84 colonic epithelial cells. J Biol Chem 271:14092–14097

    Article  PubMed  CAS  Google Scholar 

  • Xie W, Solomons KRH, Freeman S, Kaetzel MA, Bruzik KS, Nelson DJ, Shears SB (1998) Regulation of Ca2+-dependent Cl- conductance in T84 cells: cross-talk between Ins(3,4,5,6)P4 and protein phosphatases. J Physiol (Lond) 510:661–673

    Article  CAS  Google Scholar 

  • Yang L, Reece JM, Cho J, Bortner CD, Shears SB (2008) The nucleolus exhibits an osmotically regulated gatekeeping activity that controls the spatial dynamics and functions of nucleolin. J Biol Chem 283:11823–11831

    Article  PubMed  CAS  Google Scholar 

  • York JD (2006) Regulation of nuclear processes by inositol polyphosphates. Biochim Biophys Acta 1761:552–559

    Article  PubMed  CAS  Google Scholar 

  • York JD, Odom AR, Murphy R, Ives EB, Wente SR (1999) A phospholipase C-dependent inositol polyphosphate kinase pathway required for efficient messenger RNA export. Science 285:96–100

    Article  PubMed  CAS  Google Scholar 

  • York JD, Guo S, Odom AR, Spiegelberg BD, Stolz LE (2001) An expanded view of inositol signaling. Adv Enzyme Regul 41:57–71

    Article  PubMed  CAS  Google Scholar 

  • Yu X, Duan KL, Shang CF, Yu HG, Zhou Z (2004) Calcium influx through hyperpolarization-activated cation channels (I(h) channels) contributes to activity-evoked neuronal secretion. Proc Natl Acad Sci U S A 101:1051–1056

    Article  PubMed  CAS  Google Scholar 

  • Zaccolo M, Di BG, Lissandron V, Mancuso L, Terrin A, Zamparo I (2006) Restricted diffusion of a freely diffusible second messenger: mechanisms underlying compartmentalized cAMP signalling. Biochem Soc Trans 34:495–497

    Article  PubMed  CAS  Google Scholar 

  • Zhao Z, Li X, Hao J, Winston JH, Weinman SA (2007) The ClC-3 chloride transport protein traffics through the plasma membrane via interaction of an N-terminal dileucine cluster with clathrin. J Biol Chem 282:29022–29031

    Article  PubMed  CAS  Google Scholar 

  • Zhou D, Chen L-M, Hernandez L, Shears SB, Galán JE (2001) A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host-cell actin cytoskeleton rearrangements and bacterial internalization. Mol Microbiol 39:248–259

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Inositol Signaling Section, Laboratory of Signal Transduction, NIEHS, NIH, DHHS, Research Triangle Park, 27709, NC, USA, USA

    Stephen B. Shears, Sindura B. Ganapathi, Nikhil A. Gokhale, Tobias M. H. Schenk, Huanchen Wang, Jeremy D. Weaver, Angelika Zaremba & Yixing Zhou

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  1. Stephen B. Shears
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  2. Sindura B. Ganapathi
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  3. Nikhil A. Gokhale
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Correspondence to Stephen B. Shears .

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Editors and Affiliations

  1. , NICHD, National Institutes of Health, Convent Drive 49, Bethesda, 20892-4480, Maryland, USA

    Tamas Balla

  2. , Cancer- and Immunobiology, University of Basel, Mattenstrasse 28, Basel, 4058, Switzerland

    Matthias Wymann

  3. , Pharmacology and Cancer Biology, Duke University Medical Center, Durham, 27710, North Carolina, USA

    John D. York

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Shears, S.B. et al. (2012). Defining Signal Transduction by Inositol Phosphates. In: Balla, T., Wymann, M., York, J. (eds) Phosphoinositides II: The Diverse Biological Functions. Subcellular Biochemistry, vol 59. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-3015-1_13

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