inositol phosphates

Summary

Summary: Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.

Top Publications

  1. Kleinau G, Jaeschke H, Worth C, Mueller S, Gonzalez J, Paschke R, et al. Principles and determinants of G-protein coupling by the rhodopsin-like thyrotropin receptor. PLoS ONE. 2010;5:e9745 pubmed publisher
  2. Watson P, Fairall L, Santos G, Schwabe J. Structure of HDAC3 bound to co-repressor and inositol tetraphosphate. Nature. 2012;481:335-40 pubmed publisher
    ..is clearly dependent on the Ins(1,4,5,6)P(4), which may act as a regulator--potentially explaining why inositol phosphates and their kinases have been found to act as transcriptional regulators...
  3. Shears S. Diphosphoinositol polyphosphates: metabolic messengers?. Mol Pharmacol. 2009;76:236-52 pubmed publisher
    ..This review will also discuss the latest proposals concerning possible molecular mechanisms of action of this intriguing class of molecules...
  4. Sauer K, Cooke M. Regulation of immune cell development through soluble inositol-1,3,4,5-tetrakisphosphate. Nat Rev Immunol. 2010;10:257-71 pubmed publisher
    ..InsP(4)-producing kinases could therefore provide attractive drug targets for inflammatory and infectious diseases...
  5. Rasmussen S, Ingvardsen C, Torp A. Mutations in genes controlling the biosynthesis and accumulation of inositol phosphates in seeds. Biochem Soc Trans. 2010;38:689-94 pubmed publisher
    ..Understanding the biosynthetic pathway and genes controlling the accumulation of PA in plant seeds and how PA may balance the free phosphate is of importance for molecular breeding of crop plants, particularly cereals and legumes...
  6. Barker C, Illies C, Gaboardi G, Berggren P. Inositol pyrophosphates: structure, enzymology and function. Cell Mol Life Sci. 2009;66:3851-71 pubmed publisher
  7. Letcher A, Schell M, Irvine R. Do mammals make all their own inositol hexakisphosphate?. Biochem J. 2008;416:263-70 pubmed publisher
    ..Therefore claims that administrating InsP6 in the diet or applying it topically can produce health benefits by increasing extracellular InsP6 levels may require reassessment...
  8. Millard C, Watson P, Celardo I, Gordiyenko Y, Cowley S, Robinson C, et al. Class I HDACs share a common mechanism of regulation by inositol phosphates. Mol Cell. 2013;51:57-67 pubmed publisher
    ..Functional assays of both the HDAC1 and HDAC3 complexes reveal that Ins(1,4,5,6)P4 is a bona fide conserved regulator of class I HDAC complexes. ..
  9. Veiga N, Torres J, Mansell D, Freeman S, Domínguez S, Barker C, et al. "Chelatable iron pool": inositol 1,2,3-trisphosphate fulfils the conditions required to be a safe cellular iron ligand. J Biol Inorg Chem. 2009;14:51-9 pubmed publisher
    ..e. they allow iron to catalyse hydroxyl radical formation. Among small cellular molecules, certain inositol phosphates (InsPs) excel at complexing Fe(3+) in such a "safe" manner in vitro...

More Information

Publications62

  1. Ananieva E, Gillaspy G, Ely A, Burnette R, Erickson F. Interaction of the WD40 domain of a myoinositol polyphosphate 5-phosphatase with SnRK1 links inositol, sugar, and stress signaling. Plant Physiol. 2008;148:1868-82 pubmed publisher
    ..We propose that by forming a protein complex with SnRK1.1 protein, 5PTase13 plays a regulatory role linking inositol, sugar, and stress signaling...
  2. Lin H, Fridy P, Ribeiro A, Choi J, Barma D, Vogel G, et al. Structural analysis and detection of biological inositol pyrophosphates reveal that the family of VIP/diphosphoinositol pentakisphosphate kinases are 1/3-kinases. J Biol Chem. 2009;284:1863-72 pubmed publisher
    ..and Vogel, G. (1996) Biochem. J. 315, 715-725 ). Our study brings us closer to the goal of understanding the structure/function relationships that control specificity in the synthesis and biological actions of inositol pyrophosphates...
  3. Padmanabhan U, Dollins D, Fridy P, York J, Downes C. Characterization of a selective inhibitor of inositol hexakisphosphate kinases: use in defining biological roles and metabolic relationships of inositol pyrophosphates. J Biol Chem. 2009;284:10571-82 pubmed publisher
    ..of IP6K in vitro and inhibited InsP(7) and InsP(8) synthesis in vivo without affecting levels of other inositol phosphates. TNP did not inhibit either human or yeast Vip/PPIP5K, a newly described InsP(6)/InsP(7) 1/3-kinase...
  4. Losito O, Szijgyarto Z, Resnick A, Saiardi A. Inositol pyrophosphates and their unique metabolic complexity: analysis by gel electrophoresis. PLoS ONE. 2009;4:e5580 pubmed publisher
    ..Though likely involved in a wide range of cellular functions, the study of inositol pyrophosphates has suffered from a lack of readily available methods for their analysis...
  5. Onnebo S, Saiardi A. Inositol pyrophosphates modulate hydrogen peroxide signalling. Biochem J. 2009;423:109-18 pubmed publisher
    ..Furthermore, parallel cysteine mutagenesis studies performed on mammalian IP6K1 are suggestive that the ROS signal might be transduced by the direct modification of this evolutionarily conserved class of enzymes...
  6. Munnik T, Vermeer J. Osmotic stress-induced phosphoinositide and inositol phosphate signalling in plants. Plant Cell Environ. 2010;33:655-69 pubmed
    ..For several of them, a relationship to water stress has been reported. This review summarizes the current status of PPIs and IPPs in plants and discusses their potential in osmotic stress signalling and drought...
  7. Gonzalez B, Baños Sanz J, Villate M, Brearley C, Sanz Aparicio J. Inositol 1,3,4,5,6-pentakisphosphate 2-kinase is a distant IPK member with a singular inositide binding site for axial 2-OH recognition. Proc Natl Acad Sci U S A. 2010;107:9608-13 pubmed publisher
    b>Inositol phosphates (InsPs) are signaling molecules with multiple roles in cells. In particular (InsP(6)) is involved in mRNA export and editing or chromatin remodeling among other events...
  8. Chakraborty A, Koldobskiy M, Bello N, Maxwell M, Potter J, Juluri K, et al. Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain. Cell. 2010;143:897-910 pubmed publisher
    ..IP6K1 knockout mice manifest insulin sensitivity and are resistant to obesity elicited by high-fat diet or aging. Inhibition of IP6K1 may afford a therapeutic approach to obesity and diabetes...
  9. Maag D, Maxwell M, Hardesty D, Boucher K, Choudhari N, Hanno A, et al. Inositol polyphosphate multikinase is a physiologic PI3-kinase that activates Akt/PKB. Proc Natl Acad Sci U S A. 2011;108:1391-6 pubmed publisher
    ..that inositol polyphosphate multikinase (IPMK) physiologically generates PIP(3) as well as water soluble inositol phosphates. IPMK deletion reduces growth factor-elicited Akt signaling and cell proliferation caused uniquely by loss ..
  10. Aprahamian M, Bour G, Akladios C, Fylaktakidou K, Greferath R, Soler L, et al. Myo-InositolTrisPyroPhosphate treatment leads to HIF-1? suppression and eradication of early hepatoma tumors in rats. Chembiochem. 2011;12:777-83 pubmed publisher
    ..ITPP did not affect hematologic parameters during treatment. The observations of in vivo tumor eradication suggest a significant clinical potential for ITPP in cancer therapy...
  11. Sauer K, Park E, Siegemund S, French A, Wahle J, Sternberg L, et al. Inositol tetrakisphosphate limits NK cell effector functions by controlling PI3K signaling. Blood. 2013;121:286-97 pubmed publisher
    ..Our results further suggest that PI3K regulation by soluble IP(4) is a broadly important signaling paradigm...
  12. Blaabjerg K, Jørgensen H, Tauson A, Poulsen H. The presence of inositol phosphates in gastric pig digesta is affected by time after feeding a nonfermented or fermented liquid wheat- and barley-based diet. J Anim Sci. 2011;89:3153-62 pubmed publisher
    ..of digesta and evaluate the degradation of phytate or inositol hexakisphosphate (InsP(6)) and lower inositol phosphates (InsP?, InsP?, InsP?, and InsP?) in the stomach at different times after feeding pigs a fermented liquid ..
  13. Morgan K, Stavrou E, Leighton S, Miller N, Sellar R, Millar R. Elevated GnRH receptor expression plus GnRH agonist treatment inhibits the growth of a subset of papillomavirus 18-immortalized human prostate cells. Prostate. 2011;71:915-28 pubmed publisher
    ..Human metastatic prostate cancer cell growth can be inhibited by GnRH analogs but effects on virus-immortalized prostate cells have not been investigated...
  14. Jaeschke H, Kleinau G, Sontheimer J, Mueller S, Krause G, Paschke R. Preferences of transmembrane helices for cooperative amplification of G(alpha)s and G (alpha)q signaling of the thyrotropin receptor. Cell Mol Life Sci. 2008;65:4028-38 pubmed publisher
    ..Our results suggest that TMH2, 6, 7 show selective preferences towards G(alpha)s signaling, and TMH1, 2, 3, 6 for G(alpha)q signaling...
  15. Gonçalves L, Borges N, Serra F, Fernandes P, Dopazo H, Santos H. Evolution of the biosynthesis of di-myo-inositol phosphate, a marker of adaptation to hot marine environments. Environ Microbiol. 2012;14:691-701 pubmed publisher
    ..This work corroborates the view that Archaea were the first hyperthermophilic organisms...
  16. Azevedo C, Szijgyarto Z, Saiardi A. The signaling role of inositol hexakisphosphate kinases (IP6Ks). Adv Enzyme Regul. 2011;51:74-82 pubmed publisher
    ..This will hopefully precipitate the development of new ways to detect this modification, for example through the production of antibodies that specifically recognize pyrophosphorylated serines...
  17. Shears S, Gokhale N, Wang H, Zaremba A. Diphosphoinositol polyphosphates: what are the mechanisms?. Adv Enzyme Regul. 2011;51:13-25 pubmed publisher
    ..Reflecting our expectations of all teenagers, it should be our earnest hope that in the near future the diphosphoinositol polyphosphates will finally grow up. ..
  18. Sheard L, Tan X, Mao H, Withers J, Ben Nissan G, Hinds T, et al. Jasmonate perception by inositol-phosphate-potentiated COI1-JAZ co-receptor. Nature. 2010;468:400-5 pubmed publisher
    ..Our results unravel the mechanism of jasmonate perception and highlight the ability of F-box proteins to evolve as multi-component signalling hubs...
  19. Azevedo C, Burton A, Ruiz Mateos E, Marsh M, Saiardi A. Inositol pyrophosphate mediated pyrophosphorylation of AP3B1 regulates HIV-1 Gag release. Proc Natl Acad Sci U S A. 2009;106:21161-6 pubmed publisher
    ..This study identifies a cellular process that is regulated by IP(7)-mediated pyrophosphorylation...
  20. Falasca M, Chiozzotto D, Godage H, Mazzoletti M, Riley A, Previdi S, et al. A novel inhibitor of the PI3K/Akt pathway based on the structure of inositol 1,3,4,5,6-pentakisphosphate. Br J Cancer. 2010;102:104-14 pubmed publisher
    ..To further develop this compound we modified its structure to obtain more potent inhibitors of the PI3K/Akt pathway...
  21. Prasad A, Jia Y, Chakraborty A, Li Y, Jain S, Zhong J, et al. Inositol hexakisphosphate kinase 1 regulates neutrophil function in innate immunity by inhibiting phosphatidylinositol-(3,4,5)-trisphosphate signaling. Nat Immunol. 2011;12:752-60 pubmed publisher
    b>Inositol phosphates are widely produced throughout animal and plant tissues. Diphosphoinositol pentakisphosphate (InsP7) contains an energetic pyrophosphate bond...
  22. Chakraborty A, Kim S, Snyder S. Inositol pyrophosphates as mammalian cell signals. Sci Signal. 2011;4:re1 pubmed publisher
    ..These findings highlight the interplay of IPMK and IP?K in regulating growth factor and nutrient-mediated cell signaling...
  23. Sala M, Makuc D, Kolar J, Plavec J, Pihlar B. Potentiometric and ³¹P NMR studies on inositol phosphates and their interaction with iron(III) ions. Carbohydr Res. 2011;346:488-94 pubmed publisher
    ..Potentiometric and conductometric titrations of myo-inositol phosphates show that addition of iron increases acidity and consumption of hydroxide titrant...
  24. Monserrate J, York J. Inositol phosphate synthesis and the nuclear processes they affect. Curr Opin Cell Biol. 2010;22:365-73 pubmed publisher
    Recent studies have implicated inositol phosphates, a highly charged family of lipid-derived metabolites, in a slue of cellular processes. However, it is their involvement in nuclear events that has attracted much attention...
  25. Mustafa S, See H, Seeber R, Armstrong S, White C, Ventura S, et al. Identification and profiling of novel ?1A-adrenoceptor-CXC chemokine receptor 2 heteromer. J Biol Chem. 2012;287:12952-65 pubmed publisher
    ..This has important implications for the use and future development of pharmaceuticals targeting these receptors...
  26. Tello J, Newton C, Bouligand J, Guiochon Mantel A, Millar R, Young J. Congenital hypogonadotropic hypogonadism due to GnRH receptor mutations in three brothers reveal sites affecting conformation and coupling. PLoS ONE. 2012;7:e38456 pubmed publisher
    ..Together these molecular deficiencies of the two novel GNRHR1 mutations lead to the CHH phenotype when present as a compound heterozygote...
  27. Kocan M, See H, Seeber R, Eidne K, Pfleger K. Demonstration of improvements to the bioluminescence resonance energy transfer (BRET) technology for the monitoring of G protein-coupled receptors in live cells. J Biomol Screen. 2008;13:888-98 pubmed publisher
  28. Butterfield S, Tran D, Zhang H, Prestwich G, Matile S. Fluorometric detection of inositol phosphates and the activity of their enzymes with synthetic pores: discrimination of IP7 and IP6 and phytate sensing in complex matrices. J Am Chem Soc. 2008;130:3270-1 pubmed publisher
  29. Bhandari R, Juluri K, Resnick A, Snyder S. Gene deletion of inositol hexakisphosphate kinase 1 reveals inositol pyrophosphate regulation of insulin secretion, growth, and spermiogenesis. Proc Natl Acad Sci U S A. 2008;105:2349-53 pubmed publisher
    ..Male mutant mice are sterile with defects in spermiogenesis. Mutant mice are smaller than wild-type despite normal food intake. The mutants display markedly lower circulating insulin...
  30. Longo C, Wei Y, Roberts M, Miller S. Asymmetric Syntheses of L,L- and L,D-di-myo-inositol-1,1'-phosphate and their behavior as stabilizers of enzyme activity at extreme temperatures. Angew Chem Int Ed Engl. 2009;48:4158-61 pubmed publisher
    ..The differential ability of each isomer to contribute to thermoprotection in the context of a key enzyme has been assessed and both isomers of DIP are shown to possess biological activity...
  31. Miller A, Chamberlain P, Cooke M. Beyond IP3: roles for higher order inositol phosphates in immune cell signaling. Cell Cycle. 2008;7:463-7 pubmed
    ..Since this discovery, many other inositol phosphates and the kinases and phosphatases that generate these inositol phosphates have subsequently been discovered...
  32. Morgan K, Stewart A, Miller N, Mullen P, Muir M, Dodds M, et al. Gonadotropin-releasing hormone receptor levels and cell context affect tumor cell responses to agonist in vitro and in vivo. Cancer Res. 2008;68:6331-40 pubmed publisher
    ..Further studies should exploit the growth-inhibitory potential of GnRH receptor activation in abnormal cells in diseased human tissues...
  33. Burton A, Hu X, Saiardi A. Are inositol pyrophosphates signalling molecules?. J Cell Physiol. 2009;220:8-15 pubmed publisher
  34. Szijgyarto Z, Garedew A, Azevedo C, Saiardi A. Influence of inositol pyrophosphates on cellular energy dynamics. Science. 2011;334:802-5 pubmed publisher
    ..Metabolic reprogramming through inositol pyrophosphates is an evolutionary conserved mechanism that is also preserved in mammalian systems...
  35. Russell S, Siren P, Siren M, Tisdale M. Attenuation of skeletal muscle atrophy in cancer cachexia by D-myo-inositol 1,2,6-triphosphate. Cancer Chemother Pharmacol. 2009;64:517-27 pubmed publisher
    ..To determine the effectiveness of the polyanionic, metal binding agent D-myo-inositol-1,2,6-triphosphate (alpha trinositol, AT), and its hexanoyl ester (HAT), in tissue wasting in cancer cachexia...
  36. Draskovic P, Saiardi A, Bhandari R, Burton A, Ilc G, Kovacevic M, et al. Inositol hexakisphosphate kinase products contain diphosphate and triphosphate groups. Chem Biol. 2008;15:274-86 pubmed publisher
    ..We now report that IP6K synthesizes both pyrophosphate (diphospho) as well as triphospho groups on the inositol ring. All three IP6K isoforms share the same activities both in vitro and in vivo...
  37. Vetting M, Frantom P, Blanchard J. Structural and enzymatic analysis of MshA from Corynebacterium glutamicum: substrate-assisted catalysis. J Biol Chem. 2008;283:15834-44 pubmed publisher
  38. Veiga N, Torres J, Godage H, Riley A, Domínguez S, Potter B, et al. The behaviour of inositol 1,3,4,5,6-pentakisphosphate in the presence of the major biological metal cations. J Biol Inorg Chem. 2009;14:1001-13 pubmed publisher
    The inositol phosphates are ubiquitous metabolites in eukaryotes, of which the most abundant are inositol hexakisphosphate (InsP 6) and inositol 1,3,4,5,6-pentakisphosphate [Ins(1,3,4,5,6)P5)]...
  39. Leach K, Wen A, Davey A, Sexton P, Conigrave A, Christopoulos A. Identification of molecular phenotypes and biased signaling induced by naturally occurring mutations of the human calcium-sensing receptor. Endocrinology. 2012;153:4304-16 pubmed publisher
    ..A full appreciation of the molecular effects of these amino acid changes may enable the development of therapeutics that specifically target the molecular determinant of impairment in the receptor...
  40. Shears S. Understanding the biological significance of diphosphoinositol polyphosphates ('inositol pyrophosphates'). Biochem Soc Symp. 2007;:211-21 pubmed
  41. Morgan K, Sellar R, Pawson A, Lu Z, Millar R. Bovine and ovine gonadotropin-releasing hormone (GnRH)-II ligand precursors and type II GnRH receptor genes are functionally inactivated. Endocrinology. 2006;147:5041-51 pubmed
  42. Bennett M, Onnebo S, Azevedo C, Saiardi A. Inositol pyrophosphates: metabolism and signaling. Cell Mol Life Sci. 2006;63:552-64 pubmed
    ..This review aims at summarising the recent progress of our knowledge of this exciting class of molecules, from inositol pyrophosphate discovery to the description of their physiological functions...
  43. Fridy P, Otto J, Dollins D, York J. Cloning and characterization of two human VIP1-like inositol hexakisphosphate and diphosphoinositol pentakisphosphate kinases. J Biol Chem. 2007;282:30754-62 pubmed
  44. Shi Y, Azab A, Thompson M, Greenberg M. Inositol phosphates and phosphoinositides in health and disease. Subcell Biochem. 2006;39:265-92 pubmed
    In the past two decades, considerable progress has been made toward understanding inositol phosphates and PI metabolism. However, there is still much to learn...
  45. Riley A, Trusselle M, Kuad P, Borkovec M, Cho J, Choi J, et al. scyllo-inositol pentakisphosphate as an analogue of myo-inositol 1,3,4,5,6-pentakisphosphate: chemical synthesis, physicochemistry and biological applications. Chembiochem. 2006;7:1114-22 pubmed
    ..This finding both reinforces the value of scyllo-InsP(5) as a biological control and shows that the axial 2-OH group of Ins(1,3,4,5,6)P(5) plays a part in substrate recognition by PTEN and the Ins(1,3,4,5,6)P(5) 2-kinases...
  46. Sihn G, Walter T, Klein J, Queguiner I, Iwao H, Nicolau C, et al. Anti-angiogenic properties of myo-inositol trispyrophosphate in ovo and growth reduction of implanted glioma. FEBS Lett. 2007;581:962-6 pubmed
    ..These results point out the potential of ITPP for the development of a new class of anti-angiogenic and anti-cancer compounds...
  47. Azevedo C, Saiardi A. Extraction and analysis of soluble inositol polyphosphates from yeast. Nat Protoc. 2006;1:2416-22 pubmed
    ..It can easily be applied to other systems and we have included two adaptations of the protocol, one optimized for mammalian cells and the other for Arabidopsis thaliana...
  48. Jia Y, Subramanian K, Erneux C, Pouillon V, Hattori H, Jo H, et al. Inositol 1,3,4,5-tetrakisphosphate negatively regulates phosphatidylinositol-3,4,5- trisphosphate signaling in neutrophils. Immunity. 2007;27:453-67 pubmed
    ..These findings establish a role for Ins(1,3,4,5)P4 in cellular signal transduction pathways and provide another mechanism for modulating PtdIns(3,4,5)P3 signaling in neutrophils...
  49. Jackson S, Zhang Y, Haslam R, Junop M. Structural analysis of the carboxy terminal PH domain of pleckstrin bound to D-myo-inositol 1,2,3,5,6-pentakisphosphate. BMC Struct Biol. 2007;7:80 pubmed
    ..b>Inositol phosphates, which are structurally similar to phosphoinositides, are not only known to play a role as signaling ..
  50. Deleu S, Choi K, Reece J, Shears S. Pathogenicity of Salmonella: SopE-mediated membrane ruffling is independent of inositol phosphate signals. FEBS Lett. 2006;580:1709-15 pubmed
  51. Quinlan L. Phosphoinositides, inositol phosphates, and phospholipase C in embryonic stem cells. Methods Mol Biol. 2006;329:127-49 pubmed
    ..Furthermore, we describe methods of analyzing the effects of modulating the PtdIns signaling system on ES cell proliferation and the induction of apoptosis...
  52. van Sande J, Dequanter D, Lothaire P, Massart C, Dumont J, Erneux C. Thyrotropin stimulates the generation of inositol 1,4,5-trisphosphate in human thyroid cells. J Clin Endocrinol Metab. 2006;91:1099-107 pubmed
    ..Their data in FRTL-5 cells indicated no increase in inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in response to TSH. Therefore, the authors questioned results previously obtained on human cells by cruder methodology...
  53. Bao S, Bohrer A, Ramanadham S, Jin W, Zhang S, Turk J. Effects of stable suppression of Group VIA phospholipase A2 expression on phospholipid content and composition, insulin secretion, and proliferation of INS-1 insulinoma cells. J Biol Chem. 2006;281:187-98 pubmed
    ..This calls into question the generality of proposed housekeeping functions for iPLA2beta in PC homeostasis and remodeling...