Inositol pyrophosphates as mammalian cell signals

Science Signaling

Volumn 4, Issue 188, 2011, Pages

  Chakraborty, Anutosh ^a   Kim, Seyun ^a   Snyder, Solomon H ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GROWTH FACTOR; INOSITOL DERIVATIVE; INOSITOL HEXAKISPHOSPHATE KINASE; INOSITOL PHOSPHATE; INOSITOL POLYPHOSPHATE; INOSITOL PYROPHOSPHATE; INSULIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHOTRANSFERASE; PROTEIN KINASE B; PROTEIN P53; PYROPHOSPHATE; UNCLASSIFIED DRUG; INOSITOL POLYPHOSPHATE MULTIKINASE;

APOPTOSIS; BIOSYNTHESIS; DICTYOSTELIUM; ENZYME ACTIVATION; ENZYME INHIBITION; GENE; HOMEOSTASIS; INSULIN RELEASE; IPMK GENE; MAMMAL; NONHUMAN; OBESITY; PHENOTYPE; PHOSPHORYLATION; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; YEAST; ANIMAL; CARBOHYDRATE ANALYSIS; CHEMISTRY; GENETICS; HUMAN; METABOLISM; MOLECULAR GENETICS; MOUSE; PHYSIOLOGY;

DICTYOSTELIUM; MAMMALIA; MUS; MYXOGASTRIA;

ANIMALS; CARBOHYDRATE SEQUENCE; HOMEOSTASIS; HUMANS; INOSITOL PHOSPHATES; INSULIN; MICE; MOLECULAR SEQUENCE DATA; PHENOTYPE; PHOSPHOTRANSFERASES (ALCOHOL GROUP ACCEPTOR); SIGNAL TRANSDUCTION;

EID: 80052293419     PISSN: 19450877     EISSN: 19379145     Source Type: Journal    
DOI: 10.1126/scisignal.2001958     Document Type: Review

References (134)

1. H. Streb, R. F. Irvine, M. J. Berridge, I. Schulz, Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol- 1,4,5-trisphosphate. Nature 306, 67-69 (1983).
2. M. J. Berridge, P. Lipp, M. D. Bootman, The versatility and universality of calcium signalling. Nat. Rev. Mol. Cell Biol. 1, 11-21 (2000).
3. F. S. Menniti, R. N. Miller, J. W. Putney, Jr, S. B. Shears, Turnover of inositol polyphosphate pyrophosphates in pancreatoma cells. J. Biol. Chem. 268, 3850-3856 (1993).
4. L. Stephens, T. Radenberg, U. Thiel, G. Vogel, K. H. Khoo, A. Dell, T. R. Jackson, P. T. Hawkins, G. W. Mayr, The detection, purification, structural characterization, and metabolism of diphosphoinositol pentakisphosphate(s) and bisdiphosphoinositol tetrakisphosphate(s). J. Biol. Chem. 268, 4009-4015 (1993).
5. M. C. Glennon, S. B. Shears, Turnover of inositol pentakisphosphates, inositol hexakisphosphate and diphosphoinositol polyphosphates in primary cultured hepatocytes. Biochem. J. 293, 583-590 (1993).
6. S. M. Voglmaier, M. E. Bembenek, A. I. Kaplin, G. Dormán, J. D. Olszewski, G. D. Prestwich, S. H. Snyder, Purified inositol hexakisphosphate kinase is an ATP synthase:Diphosphoinositol pentakisphosphate as a high-energy phosphate donor. Proc. Natl. Acad. Sci. U.S.A. 93, 4305-4310 (1996).
7. A. Saiardi, H. Erdjument-Bromage, A. M. Snowman, P. Tempst, S. H. Snyder, Synthesis of diphosphoinositol pentakisphosphate by a newly identified family of higher inositol polyphosphate kinases. Curr. Biol. 9, 1323-1326 (1999).
8. M. J. Schell, A. J. Letcher, C. A. Brearley, J. Biber, H. Murer, R. F. Irvine, PiUS (Pi uptake stimulator) is an inositol hexakisphosphate kinase. FEBS Lett. 461, 169-172 (1999).
9. A. Saiardi, E. Nagata, H. R. Luo, A. M. Snowman, S. H. Snyder, Identification and characterization of a novel inositol hexakisphosphate kinase. J. Biol. Chem. 276, 39179-39185 (2001).
10. R. Bhandari, K. R. Juluri, A. C. Resnick, S. H. Snyder, Gene deletion of inositol hexakisphosphate kinase 1 reveals inositol pyrophosphate regulation of insulin secretion, growth, and spermiogenesis. Proc. Natl. Acad. Sci. U.S.A. 105, 2349-2353 (2008).
11. A. Chakraborty, M. A. Koldobskiy, N. T. Bello, M. Maxwell, J. J. Potter, K. R. Juluri, D. Maag, S. Kim, A. S. Huang, M. J. Dailey, M. Saleh, A. M. Snowman, T. H. Moran, E. Mezey, S. H. Snyder, Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain. Cell 143, 897-910 (2010).
12. A. Prasad, Y. Jia, A. Chakraborty, Y. Li, S. K. Jain, J. Zhong, S. G. Roy, F. Loison, S. Mondal, J. Sakai, C. Blanchard, S. H. Snyder, H. R. Luo, Inositol hexakisphosphate kinase 1 regulates neutrophil function in innate immunity by inhibiting phosphatidylinositol-(3,4,5)-trisphosphate signaling. Nat. Immunol. 12, 752-760 (2011).
13. M. A. Koldobskiy, A. Chakraborty, J. K. Werner, Jr, A. M. Snowman, K. R. Juluri, M. S. Vandiver, S. Kim, S. Heletz, S. H. Snyder, p53-mediated apoptosis requires inositol hexakisphosphate kinase-2. Proc. Natl. Acad. Sci. U.S.A. 107, 20947-20951 (2010).
14. B. H. Morrison, R. Haney, E. Lamarre, J. Drazba, G. D. Prestwich, D. J. Lindner, Gene deletion of inositol hexakisphosphate kinase 2 predisposes to aerodigestive tract carcinoma. Oncogene 28, 2383-2392 (2009).
15. C. Albert, S. T. Safrany, M. E. Bembenek, K. M. Reddy, K. Reddy, J. Falck, M. Bröcker, S. B. Shears, G. W. Mayr, Biological variability in the structures of diphosphoinositol polyphosphates in Dictyostelium discoideum and mammalian cells. Biochem. J. 327, 553-560 (1997).
16. H. Lin, P. C. Fridy, A. A. Ribeiro, J. H. Choi, D. K. Barma, G. Vogel, J. R. Falck, S. B. Shears, J. D. York, G. W. Mayr, Structural analysis and detection of biological inositol pyrophosphates reveal that the family of VIP/diphosphoinositol pentakisphosphate kinases are 1/3-kinases. J. Biol. Chem. 284, 1863-1872 (2009).
17. S. Mulugu, W. Bai, P. C. Fridy, R. J. Bastidas, J. C. Otto, D. E. Dollins, T. A. Haystead, A. A. Ribeiro, J. D. York, A conserved family of enzymes that phosphorylate inositol hexakisphosphate. Science 316, 106-109 (2007).
18. Y. S. Lee, S. Mulugu, J. D. York, E. K. O'Shea, Regulation of a cyclin-CDK-CDK inhibitor complex by inositol pyrophosphates. Science 316, 109-112 (2007).
19. J. H. Choi, J. Williams, J. Cho, J. R. Falck, S. B. Shears, Purification, sequencing, and molecular identification of a mammalian PP-InsP5 kinase that is activated when cells are exposed to hyperosmotic stress. J. Biol. Chem. 282, 30763-30775 (2007).
20. P. C. Fridy, J. C. Otto, D. E. Dollins, J. D. York, Cloning and characterization of two human VIP1-like inositol hexakisphosphate and diphosphoinositol pentakisphosphate kinases. J. Biol. Chem. 282, 30754-30762 (2007).
21. J. Bercy, E. Dubois, F. Messenguy, Regulation of arginine metabolism in Saccharomyces cerevisiae:Expression of the three ARGR regulatory genes and cellular localization of their products. Gene 55, 277-285 (1987).
22. N. Amar, F. Messenguy, M. El Bakkoury, E. Dubois, ArgRII, a component of the ArgR-Mcm1 complex involved in the control of arginine metabolism in Saccharomyces cerevisiae, is the sensor of arginine. Mol. Cell. Biol. 20, 2087-2097 (2000).
23. A. R. Odom, A. Stahlberg, S. R. Wente, J. D. York, A role for nuclear inositol 1,4,5-trisphosphate kinase in transcriptional control. Science 287, 2026-2029 (2000).
24. J. P. Frederick, D. Mattiske, J. A. Wofford, L. C. Megosh, L. Y. Drake, S. T. Chiou, B. L. Hogan, J. D. York, 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 (2005).
25. A. C. Resnick, A. M. Snowman, B. N. Kang, K. J. Hurt, S. H. Snyder, A. Saiardi, Inositol polyphosphate multikinase is a nuclear PI3-kinase with transcriptional regulatory activity. Proc. Natl. Acad. Sci. U.S.A. 102, 12783-12788 (2005).
26. D. Maag, M. J. Maxwell, D. A. Hardesty, K. L. Boucher, N. Choudhari, A. G. Hanno, J. F. Ma, A. S. Snowman, J. W. Pietropaoli, R. Xu, P. B. Storm, A. Saiardi, S. H. Snyder, A. C. Resnick, Inositol polyphosphate multikinase is a physiologic PI3-kinase that activates Akt/PKB. Proc. Natl. Acad. Sci. U.S.A. 108, 1391-1396 (2011).
27. S. Kim, S. F. Kim, D. Maag, M. J. Maxwell, A. C. Resnick, K. R. Juluri, A. Chakraborty, M. A. Koldobskiy, S. H. Cha, R. Barrow, A. M. Snowman, S. H. Snyder, Amino acid signaling to mTOR mediated by inositol polyphosphate multikinase. Cell Metab. 13, 215-221 (2011).
28. R. F. Irvine, M. J. Schell, Back in the water:The return of the inositol phosphates. Nat. Rev. Mol. Cell Biol. 2, 327-338 (2001).
29. S. B. Shears, How versatile are inositol phosphate kinases? Biochem. J. 377, 265-280 (2004).
30. M. Bennett, S. M. Onnebo, C. Azevedo, A. Saiardi, Inositol pyrophosphates:Metabolism and signaling. Cell. Mol. Life Sci. 63, 552-564 (2006).
31. S. B. Shears, Diphosphoinositol polyphosphates:Metabolic messengers? Mol. Pharmacol. 76, 236-252 (2009).
32. C. J. Barker, C. Illies, G. C. Gaboardi, P. O. Berggren, Inositol pyrophosphates:Structure, enzymology and function. Cell. Mol. Life Sci. 66, 3851-3871 (2009).
33. R. F. Irvine, A. J. Letcher, J. P. Heslop, M. J. Berridge, The inositol tris/tetrakisphosphate pathway - Demonstration of Ins(1,4,5)P3 3- Kinase activity in animal tissues. Nature 320, 631-634 (1986).
34. J. A. Chattaway, B. K. Drobak, P. A. C. Watkins, A. P. Dawson, A. J. Letcher, L. R. Stephens, R. F. Irvine, An inositol 1,4,5-trisphosphate 6-kinase activity in pea roots. Planta 187, 542-545 (1992).
35. J. Stevenson-Paulik, A. R. Odom, J. D. York, Molecular and biochemical characterization of two plant inositol polyphosphate 6-/3-/5-kinases. J. Biol. Chem. 277, 42711-42718 (2002).
36. A. Saiardi, J. J. Caffrey, S. H. Snyder, S. B. Shears, Inositol polyphosphate multikinase (ArgRIII) determines nuclear mRNA export in Saccharomyces cerevisiae. FEBS Lett. 468, 28-32 (2000).
37. G. N. Europe-Finner, B. Gammon, P. C. Newell, Accumulation of [3H]-inositol into inositol polyphosphates during development of Dictyostelium. Biochem. Biophys. Res. Commun. 181, 191-196 (1991).
38. L. R. Stephens, P. T. Hawkins, A. F. Stanley, T. Moore, D. R. Poyner, P. J. Morris, M. R. Hanley, R. R. Kay, R. F. Irvine, myo-inositol pentakisphosphates. Structure, biological occurrence and phosphorylation to myo-inositol hexakisphosphate. Biochem. J. 275, 485-499 (1991).
39. K. G. Oliver, J. W. Putney Jr, J. F. Obie, S. B. Shears, The interconversion of inositol 1,3,4,5,6-pentakisphosphate and inositol tetrakisphosphates in AR4-2J cells. J. Biol. Chem. 267, 21528-21534 (1992).
40. N. S. Wong, C. J. Barker, A. J. Morris, A. Craxton, C. J. Kirk, R. H. Michell, The inositol phosphates in WRK1 rat mammary tumour cells. Biochem. J. 286, 459-468 (1992).
41. G. W. Mayr, T. Radenberg, U. Thiel, G. Vogel, L. R. Stephens, Phosphoinositol diphosphates:Nonenzymic formation in vitro and occurrence in vivo in the cellular slime mold Dictyostelium. Carbohydr. Res. 234, 247-262 (1992).
42. S. B. Shears, N. Ali, A. Craxton, M. E. Bembenek, Synthesis and metabolism of bis-diphosphoinositol tetrakisphosphate in vitro and in vivo. J. Biol. Chem. 270, 10489-10497 (1995).
43. P. Draskovic, A. Saiardi, R. Bhandari, A. Burton, G. Ilc, M. Kovacevic, S. H. Snyder, M. Podobnik, Inositol hexakisphosphate kinase products contain diphosphate and triphosphate groups. Chem. Biol. 15, 274-286 (2008).
44. J. W. Verbsky, M. P. Wilson, M. V. Kisseleva, P. W. Majerus, S. R. Wente, The synthesis of inositol hexakisphosphate. Characterization of human inositol 1,3,4,5,6-pentakisphosphate 2-kinase. J. Biol. Chem. 277, 31857-31862 (2002).
45. A. M. Seeds, R. J. Bastidas, J. D. York, Molecular definition of a novel inositol polyphosphate metabolic pathway initiated by inositol 1,4,5-trisphosphate 3-kinase activity in Saccharomyces cerevisiae. J. Biol. Chem. 280, 27654-27661 (2005).
46. A. Saiardi, J. J. Caffrey, S. H. Snyder, S. B. Shears, The inositol hexakisphosphate kinase family. Catalytic flexibility and function in yeast vacuole biogenesis. J. Biol. Chem. 275, 24686-24692 (2000).
47. S. T. Safrany, J. J. Caffrey, X. Yang, M. E. Bembenek, M. B. Moyer, W. A. Burkhart, S. B. Shears, A novel context for the 'MutT' module, a guardian of cell integrity, in a diphosphoinositol polyphosphate phosphohydrolase. EMBO J. 17, 6599-6607 (1998).
48. D. I. Fisher, S. T. Safrany, P. Strike, A. G. McLennan, J. L. Cartwright, Nudix hydrolases that degrade dinucleoside and diphosphoinositol polyphosphates also have 5-phosphoribosyl 1-pyrophosphate (PRPP) pyrophosphatase activity that generates the glycolytic activator ribose 1,5-bisphosphate. J. Biol. Chem. 277, 47313-47317 (2002).
49. S. W. Ingram, S. T. Safrany, L. D. Barnes, Disruption and overexpression of the Schizosaccharomyces pombe aps1 gene, and effects on growth rate, morphology and intracellular diadenosine 5′,5′-P1,P5-pentaphosphate and diphosphoinositol polyphosphate concentrations. Biochem. J. 369, 519-528 (2003).
50. C. Illies, J. Gromada, R. Fiume, B. Leibiger, J. Yu, K. Juhl, S. N. Yang, D. K. Barma, J. R. Falck, A. Saiardi, C. J. Barker, P. O. Berggren, Requirement of inositol pyrophosphates for full exocytotic capacity in pancreatic beta cells. Science 318, 1299-1302 (2007).
51. B. S. Szwergold, R. A. Graham, T. R. Brown, Observation of inositol pentakis- and hexakisphosphates in mammalian tissues by 31P NMR. Biochem. Biophys. Res. Commun. 149, 874-881 (1987).
52. T. Laussmann, C. Pikzack, U. Thiel, G. W. Mayr, G. Vogel, Diphospho-myo-inositol phosphates during the life cycle of Dictyostelium and Polysphondylium. Eur. J. Biochem. 267, 2447-2451 (2000).
53. X. Pesesse, K. Choi, T. Zhang, S. B. Shears, Signaling by higher inositol polyphosphates. Synthesis of bisdiphosphoinositol tetrakisphosphate ("InsP8") is selectively activated by hyperosmotic stress. J. Biol. Chem. 279, 43378-43381 (2004).
54. S. T. Safrany, Protocols for regulation and study of diphosphoinositol polyphosphates. Mol. Pharmacol. 66, 1585-1591 (2004).
55. K. Choi, E. Mollapour, S. B. Shears, Signal transduction during environmental stress:InsP8 operates within highly restricted contexts. Cell. Signal. 17, 1533-1541 (2005).
56. K. Choi, E. Mollapour, J. H. Choi, S. B. Shears, Cellular energetic status supervises the synthesis of bis-diphosphoinositol tetrakisphosphate independently of AMP-activated protein kinase. Mol. Pharmacol. 74, 527-536 (2008).
57. E. Nagata, H. R. Luo, A. Saiardi, B. I. Bae, N. Suzuki, S. H. Snyder, Inositol hexakisphosphate kinase-2, a physiologic mediator of cell death. J. Biol. Chem. 280, 1634-1640 (2005).
58. A. Chakraborty, M. A. Koldobskiy, K. M. Sixt, K. R. Juluri, A. K. Mustafa, A. M. Snowman, D. B. Van Rossum, R. L. Patterson, S. H. Snyder, HSP90 regulates cell survival via inositol hexakisphosphate kinase-2. Proc. Natl. Acad. Sci. U.S.A. 105, 1134-1139 (2008).
59. A. Chakraborty, J. K. Werner, Jr, M. A. Koldobskiy, A. K. Mustafa, K. R. Juluri, J. Pietropaoli, A. M. Snowman, S. H. Snyder, Casein kinase-2 mediates cell survival through phosphorylation and degradation of inositol hexakisphosphate kinase-2. Proc. Natl. Acad. Sci. U.S.A. 108, 2205-2209 (2011).
60. D. M. Blakeley, A. N. Corps, K. D. Brown, Bombesin and platelet-derived growth factor stimulate formation of inositol phosphates and Ca2+ mobilization in Swiss 3T3 cells by different mechanisms. Biochem. J. 258, 177-185 (1989).
61. B. C. Tilly, P. A. Van Paridon, I. Verlaan, S. W. De Laat, W. H. Moolenaar, Epidermal-growth-factor-induced formation of inositol phosphates in human A431 cells. Differences from the effect of bradykinin. Biochem. J. 252, 857-863 (1988).
62. N. Takasu, M. Takasu, I. Komiya, Y. Nagasawa, T. Asawa, Y. Shimizu, T. Yamada, Insulin-like growth factor I stimulates inositol phosphate accumulation, a rise in cytoplasmic free calcium, and proliferation in cultured porcine thyroid cells. J. Biol. Chem. 264, 18485-18488 (1989).
63. T. Balla, S. S. Sim, A. J. Baukal, S. G. Rhee, K. J. Catt, Inositol polyphosphates are not increased by overexpression of Ins(1,4,5)P3 3-kinase but show cell-cycle dependent changes in growth factor-stimulated fibroblasts. Mol. Biol. Cell 5, 17-27 (1994).
64. Y. Gao, H. Y. Wang, Inositol pentakisphosphate mediates Wnt/beta-catenin signaling. J. Biol. Chem. 282, 26490-26502 (2007).
65. C. Y. Logan, R. Nusse, The Wnt signaling pathway in development and disease. Annu. Rev. Cell Dev. Biol. 20, 781-810 (2004).
66. P. W. Majerus, Inositol phosphate biochemistry. Annu. Rev. Biochem. 61, 225-250 (1992).
67. A. R. Alcázar-Román, S. R. Wente, Inositol polyphosphates:A new frontier for regulating gene expression. Chromosoma 117, 1-13 (2008).
68. M. Fukuda, T. Kojima, H. Kabayama, K. Mikoshiba, Mutation of the pleckstrin homology domain of Bruton's tyrosine kinase in immunodeficiency impaired inositol 1,3,4,5-tetrakisphosphate binding capacity. J. Biol. Chem. 271, 30303-30306 (1996).
69. M. Hirata, T. Kanematsu, H. Takeuchi, H. Yagisawa, Pleckstrin homology domain as an inositol compound binding module. Jpn. J. Pharmacol. 76, 255-263 (1998).
70. W. Ye, N. Ali, M. E. Bembenek, S. B. Shears, E. M. Lafer, Inhibition of clathrin assembly by high affinity binding of specific inositol polyphosphates to the synapse-specific clathrin assembly protein AP-3. J. Biol. Chem. 270, 1564-1568 (1995).
71. Y. H. Huang, J. A. Grasis, A. T. Miller, R. Xu, S. Soonthornvacharin, A. H. Andreotti, C. D. Tsoukas, M. P. Cooke, K. Sauer, Positive regulation of Itk PH domain function by soluble IP4. Science 316, 886-889 (2007).
72. Y. Jia, K. K. Subramanian, C. Erneux, V. Pouillon, H. Hattori, H. Jo, J. You, D. Zhu, S. Schurmans, H. R. Luo, Inositol 1,3,4,5-tetrakisphosphate negatively regulates phosphatidylinositol-3,4,5-trisphosphate signaling in neutrophils. Immunity 27, 453-467 (2007).
73. H. R. Luo, Y. E. Huang, J. C. Chen, A. Saiardi, M. Iijima, K. Ye, Y. Huang, E. Nagata, P. Devreotes, S. H. Snyder, Inositol pyrophosphates mediate chemotaxis in Dictyostelium via pleckstrin homology domain-PtdIns(3,4,5)P3 interactions. Cell 114, 559-572 (2003).
74. H. Takeuchi, T. Kanematsu, Y. Misumi, F. Sakane, H. Konishi, U. Kikkawa, Y. Watanabe, M. Katan, M. Hirata, Distinct specificity in the binding of inositol phosphates by pleckstrin homology domains of pleckstrin, RAC-protein kinase, diacylglycerol kinase and a new 130 kDa protein. Biochim. Biophys. Acta 1359, 275-285 (1997).
75. M. Frech, M. Andjelkovic, E. Ingley, K. K. Reddy, J. R. Falck, B. A. Hemmings, High affinity binding of inositol phosphates and phosphoinositides to the pleckstrin homology domain of RAC/protein kinase B and their influence on kinase activity. J. Biol. Chem. 272, 8474-8481 (1997).
76. D. Komander, A. Fairservice, M. Deak, G. S. Kular, A. R. Prescott, C. Peter Downes, S. T. Safrany, D. R. Alessi, D. M. Van Aalten, Structural insights into the regulation of PDK1 by phosphoinositides and inositol phosphates. EMBO J. 23, 3918-3928 (2004).
77. M. A. Lemmon, Membrane recognition by phospholipid- binding domains. Nat. Rev. Mol. Cell Biol. 9, 99-111 (2008).
78. D. A. Fruman, L. E. Rameh, L. C. Cantley, Phosphoinositide binding domains:Embracing 3-phosphate. Cell 97, 817-820 (1999).
79. G. Di Paolo, P. De Camilli, Phosphoinositides in cell regulation and membrane dynamics. Nature 443, 651-657 (2006).
80. B. D. Manning, L. C. Cantley, AKT/PKB signaling:Navigating downstream. Cell 129, 1261-1274 (2007).
81. Y. S. Lee, K. Huang, F. A. Quiocho, E. K. O'Shea, Molecular basis of cyclin-CDK-CKI regulation by reversible binding of an inositol pyrophosphate. Nat. Chem. Biol. 4, 25-32 (2008).
82. T. Laussmann, R. Eujen, C. M. Weisshuhn, U. Thiel, G. Vogel, Structures of diphospho-myoinositol pentakisphosphate and bisdiphosphomyo- inositol tetrakisphosphate from Dictyostelium resolved by NMR analysis. Biochem. J. 315, 715-720 (1996).
83. A. Saiardi, R. Bhandari, A. C. Resnick, A. M. Snowman, S. H. Snyder, Phosphorylation of proteins by inositol pyrophosphates. Science 306, 2101-2105 (2004).
84. R. Bhandari, A. Saiardi, Y. Ahmadibeni, A. M. Snowman, A. C. Resnick, T. Z. Kristiansen, H. Molina, A. Pandey, J. K. Werner Jr, K. R. Juluri, Y. Xu, G. D. Prestwich, K. Parang, S. H. Snyder, Protein pyrophosphorylation by inositol pyrophosphates is a posttranslational event. Proc. Natl. Acad. Sci. U.S.A. 104, 15305-15310 (2007).
85. C. Azevedo, A. Burton, E. Ruiz-Mateos, M. Marsh, A. Saiardi, Inositol pyrophosphate mediated pyrophosphorylation of AP3B1 regulates HIV-1 Gag release. Proc. Natl. Acad. Sci. U.S.A. 106, 21161-21166 (2009).
86. A. Kobir, L. Shi, A. Boskovic, C. Grangeasse, D. Franjevic, I. Mijakovic, Protein phosphorylation in bacterial signal transduction. Biochim. Biophys. Acta (2011); 10.1016/j.bbagen.2011.01.006.
87. C. E. Hand, J. F. Honek, Phosphate transfer from inositol pyrophosphates InsP5PP and InsP4(PP)2:A semi-empirical investigation. Bioorg. Med. Chem. Lett. 17, 183-188 (2007).
88. A. Saiardi, A. C. Resnick, A. M. Snowman, B. Wendland, S. H. Snyder, Inositol pyrophosphates regulate cell death and telomere length through phosphoinositide 3-kinase-related protein kinases. Proc. Natl. Acad. Sci. U.S.A. 102, 1911-1914 (2005).
89. S. J. York, B. N. Armbruster, P. Greenwell, T. D. Petes, J. D. York, Inositol diphosphate signaling regulates telomere length. J. Biol. Chem. 280, 4264-4269 (2005).
90. H. R. Luo, A. Saiardi, H. Yu, E. Nagata, K. Ye, S. H. Snyder, Inositol pyrophosphates are required for DNA hyperrecombination in protein kinase c1 mutant yeast. Biochemistry 41, 2509-2515 (2002).
91. E. Dubois, B. Scherens, F. Vierendeels, M. M. Ho, F. Messenguy, S. B. Shears, In Saccharomyces cerevisiae, the inositol polyphosphate kinase activity of Kcs1p is required for resistance to salt stress, cell wall integrity, and vacuolar morphogenesis. J. Biol. Chem. 277, 23755-23763 (2002).
92. A. Saiardi, C. Sciambi, J. M. McCaffery, B. Wendland, S. H. Snyder, Inositol pyrophosphates regulate endocytic trafficking. Proc. Natl. Acad. Sci. U.S.A. 99, 14206-14211 (2002).
93. J. Pöhlmann, U. Fleig, Asp1, a conserved 1/3 inositol polyphosphate kinase, regulates the dimorphic switch in Schizosaccharomyces pombe. Mol. Cell. Biol. 30, 4535-4547 (2010).
94. H. R. Luo, A. Saiardi, E. Nagata, K. Ye, H. Yu, T. S. Jung, X. Luo, S. Jain, A. Sawa, S. H. Snyder, GRAB:A physiologic guanine nucleotide exchange factor for Rab3A, which interacts with inositol hexakisphosphate kinase. Neuron 31, 439-451 (2001).
95. B. H. Morrison, J. A. Bauer, D. V. Kalvakolanu, D. J. Lindner, Inositol hexakisphosphate kinase 2 mediates growth suppressive and apoptotic effects of interferon-beta in ovarian carcinoma cells. J. Biol. Chem. 276, 24965-24970 (2001).
96. B. H. Morrison, J. A. Bauer, J. Hu, R. W. Grane, A. M. Ozdemir, M. Chawla-Sarkar, B. Gong, A. Almasan, D. V. Kalvakolanu, D. J. Lindner, Inositol hexakisphosphate kinase 2 sensitizes ovarian carcinoma cells to multiple cancer therapeutics. Oncogene 21, 1882-1889 (2002).
97. B. H. Morrison, Z. Tang, B. S. Jacobs, J. A. Bauer, D. J. Lindner, Apo2L/TRAIL induction and nuclear translocation of inositol hexakisphosphate kinase 2 during IFN-beta-induced apoptosis in ovarian carcinoma. Biochem. J. 385, 595-603 (2005).
98. D. Mahalingam, E. Szegezdi, M. Keane, S. De Jong, A. Samali, TRAIL receptor signalling and modulation:Are we on the right TRAIL? Cancer Treat. Rev. 35, 280-288 (2009).
99. P. P. Scaglioni, T. M. Yung, L. F. Cai, H. Erdjument- Bromage, A. J. Kaufman, B. Singh, J. Teruya- Feldstein, P. Tempst, P. P. Pandolfi, A CK2-dependent mechanism for degradation of the PML tumor suppressor. Cell 126, 269-283 (2006).
100. M. Ruzzene, L. A. Pinna, Addiction to protein kinase CK2:A common denominator of diverse cancer cells? Biochim. Biophys. Acta 1804, 499-504 (2010).
101. A. V. Ljubimov, S. Caballero, A. M. Aoki, L. A. Pinna, M. B. Grant, R. Castellon, Involvement of protein kinase CK2 in angiogenesis and retinal neovascularization. Invest. Ophthalmol. Vis. Sci. 45, 4583-4591 (2004).
102. E. Nagata, A. Saiardi, H. Tsukamoto, T. Satoh, Y. Itoh, J. Itoh, M. Shibata, S. Takizawa, S. Takagi, Inositol hexakisphosphate kinases promote autophagy. Int. J. Biochem. Cell Biol. 42, 2065-2071 (2010).
103. S. M. Onnebo, A. Saiardi, Inositol pyrophosphates modulate hydrogen peroxide signalling. Biochem. J. 423, 109-118 (2009).
104. B. Sarmah, S. R. Wente, Inositol hexakisphosphate kinase-2 acts as an effector of the vertebrate Hedgehog pathway. Proc. Natl. Acad. Sci. U.S.A. 107, 19921-19926 (2010).
105. Y. Izumiya, T. Hopkins, C. Morris, K. Sato, L. Zeng, J. Viereck, J. A. Hamilton, N. Ouchi, N. K. LeBrasseur, K. Walsh, Fast/Glycolytic muscle fiber growth reduces fat mass and improves metabolic parameters in obese mice. Cell Metab. 7, 159-172 (2008).
106. X. D. Peng, P. Z. Xu, M. L. Chen, A. Hahn-Windgassen, J. Skeen, J. Jacobs, D. Sundararajan, W. S. Chen, S. E. Crawford, K. G. Coleman, N. Hay, Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2. Genes Dev. 17, 1352-1365 (2003).
107. S. E. Ross, N. Hemati, K. A. Longo, C. N. Bennett, P. C. Lucas, R. L. Erickson, O. A. MacDougald, Inhibition of adipogenesis by Wnt signaling. Science 289, 950-953 (2000).
108. Q. Q. Tang, M. Grønborg, H. Huang, J. W. Kim, T. C. Otto, A. Pandey, M. D. Lane, Sequential phosphorylation of CCAAT enhancer-binding protein beta by MAPK and glycogen synthase kinase 3beta is required for adipogenesis. Proc. Natl. Acad. Sci. U.S.A. 102, 9766-9771 (2005).
109. K. Funai, J. D. Parkington, S. Carambula, R. A. Fielding, Age-associated decrease in contraction- induced activation of downstream targets of Akt/mTor signaling in skeletal muscle. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290, R1080-R1086 (2006).
110. J. Shao, H. Yamashita, L. Qiao, J. E. Friedman, Decreased Akt kinase activity and insulin resistance in C57BL/KsJ-Leprdb/db mice. J. Endocrinol. 167, 107-115 (2000).
111. O. Kaidanovich, H. Eldar-Finkelman, The role of glycogen synthase kinase-3 in insulin resistance and type 2 diabetes. Expert Opin. Ther. Targets 6, 555-561 (2002).
112. U. Padmanabhan, D. E. Dollins, P. C. Fridy, J. D. York, C. P. Downes, Characterization of a selective inhibitor of inositol hexakisphosphate kinases:Use in defining biological roles and metabolic relationships of inositol pyrophosphates. J. Biol. Chem. 284, 10571-10582 (2009).
113. C. P. Downes, A. Gray, A. Fairservice, S. T. Safrany, I. H. Batty, I. Fleming, The regulation of membrane to cytosol partitioning of signalling proteins by phosphoinositides and their soluble headgroups. Biochem. Soc. Trans. 33, 1303-1307 (2005).
114. V. Calleja, D. Alcor, M. Laguerre, J. Park, B. Vojnovic, B. A. Hemmings, J. Downward, P. J. Parker, B. Larijani, Intramolecular and intermolecular interactions of protein kinase B define its activation in vivo. PLoS Biol. 5, e95 (2007).
115. S. G. Jackson, S. Al-Saigh, C. Schultz, M. S. Junop, Inositol pentakisphosphate isomers bind PH domains with varying specificity and inhibit phosphoinositide interactions. BMC Struct. Biol. 11, 11 (2011).
116. N. A. Gokhale, A. Zaremba, S. B. Shears, Receptor- dependent compartmentalization of PPIP5K1, a kinase with a cryptic polyphosphoinositide binding domain. Biochem. J. 434, 415-426 (2011).
117. J. D. Carpten, A. L. Faber, C. Horn, G. P. Donoho, S. L. Briggs, C. M. Robbins, G. Hostetter, S. Boguslawski, T. Y. Moses, S. Savage, M. Uhlik, A. Lin, J. Du, Y. W. Qian, D. J. Zeckner, G. Tucker-Kellogg, J. Touchman, K. Patel, S. Mousses, M. Bittner, R. Schevitz, M. H. Lai, K. L. Blanchard, J. E. Thomas, A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature 448, 439-444 (2007).
118. L. Stephens, C. Ellson, P. Hawkins, Roles of PI3Ks in leukocyte chemotaxis and phagocytosis. Curr. Opin. Cell Biol. 14, 203-213 (2002).
119. T. S. Olson, K. Ley, Chemokines and chemokine receptors in leukocyte trafficking. Am. J. Physiol. Regul. Integr. Comp. Physiol. 283, R7-R28 (2002).
120. P. T. Hawkins, K. Davidson, L. R. Stephens, The role of PI3Ks in the regulation of the neutrophil NADPH oxidase. Biochem. Soc. Symp. 74, 59-67 (2007).
121. E. S. Emamian, D. Hall, M. J. Birnbaum, M. Karayiorgou, J. A. Gogos, Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. Nat. Genet. 36, 131-137 (2004).
122. R. S. Jope, Lithium and GSK-3:One inhibitor, two inhibitory actions, multiple outcomes. Trends Pharmacol. Sci. 24, 441-443 (2003).
123. J. M. Beaulieu, S. Marion, R. M. Rodriguiz, I. O. Medvedev, T. D. Sotnikova, V. Ghisi, W. C. Wetsel, R. J. Lefkowitz, R. R. Gainetdinov, M. G. Caron, A beta-arrestin 2 signaling complex mediates lithium action on behavior. Cell 132, 125-136 (2008).
124. E. Piccolo, S. Vignati, T. Maffucci, P. F. Innominato, A. M. Riley, B. V. Potter, P. P. Pandolfi, M. Broggini, S. Iacobelli, P. Innocenti, M. Falasca, Inositol pentakisphosphate promotes apoptosis through the PI 3-K/Akt pathway. Oncogene 23, 1754-1765 (2004).
125. M. Falasca, D. Chiozzotto, H. Y. Godage, M. Mazzoletti, A. M. Riley, S. Previdi, B. V. Potter, M. Broggini, T. Maffucci, A novel inhibitor of the PI3K/Akt pathway based on the structure of inositol 1,3,4,5,6-pentakisphosphate. Br. J. Cancer 102, 104-114 (2010).
126. J. Heitman, N. R. Movva, M. N. Hall, Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 253, 905-909 (1991).
127. D. M. Sabatini, H. Erdjument-Bromage, M. Lui, P. Tempst, S. H. Snyder, RAFT1:A mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell 78, 35-43 (1994).
128. X. M. Ma, J. Blenis, Molecular mechanisms of mTOR-mediated translational control. Nat. Rev. Mol. Cell Biol. 10, 307-318 (2009).
129. D. H. Kim, D. D. Sarbassov, S. M. Ali, J. E. King, R. R. Latek, H. Erdjument-Bromage, P. Tempst, D. M. Sabatini, mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110, 163-175 (2002).
130. D. D. Sarbassov, S. M. Ali, D.-H. Kim, D. A. Guertin, R. R. Latek, H. Erdjument-Bromage, P. Tempst, D. M. Sabatini, Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr. Biol. 14, 1296-1302 (2004).
131. K. M. Reddy, K. K. Reddy, J. R. Falck, Synthesis of 2- and 5-diphospho-myo-inositol pentakisphosphate (2- and 5-PP-InsP5), intracellular mediators. Tetrahedron Lett. 38, 4951-4952 (1997).
132. H. Zhang, J. Thompson, G. D. Prestwich, A scalable synthesis of the IP7 isomer, 5-PP-Ins(1,2,3,4,6) P5. Org. Lett. 11, 1551-1554 (2009).
133. O. Losito, Z. Szijgyarto, A. C. Resnick, A. Saiardi, Inositol pyrophosphates and their unique metabolic complexity:Analysis by gel electrophoresis. PLoS ONE 4, e5580 (2009).
134. Acknowledgments: We thank M. Koldobskiy, R. Tyagi, K. Juluri, J. Xu, J. K. Werner, J. Cha, D. Maag, M. Maxwell, R. Xu, and F. Rao for valued contributions. Funding: This work was supported by U.S. Public Health Service Grants MH18501 and DA-000266 (to S.H.S.). Competing interests: S.H.S. is on the Scientific Advisory Board of Cerecor, Inc., which may eventually do research related to inositol phosphates.