Diphosphoinositol Polyphosphates: Metabolic Messengers?

  1. Stephen B. Shears
  1. Inositide Signaling Group, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina
  1. Address correspondence to:
    Stephen Shears, Inositide Signaling Group, National Institute of Environmental Health Sciences, NIH, DHHS, PO Box 12233, Research Triangle Park, NC 27709. E-mail: shears{at}niehs.nih.gov

Abstract

The diphosphoinositol polyphosphates (“inositol pyrophosphates”) are a specialized subgroup of the inositol phosphate signaling family. This review proposes that many of the current data concerning the metabolic turnover and biological effects of the diphosphoinositol polyphosphates are linked by a common theme: these polyphosphates act as metabolic messengers. This review will also discuss the latest proposals concerning possible molecular mechanisms of action of this intriguing class of molecules.

Footnotes

  • This work was supported by the Intramural Research Program of the National Institutes of Health National Institute of Environmental Health Sciences.

  • ABBREVIATIONS: 5-PP-InsP5, 5-diphospho-d-myo-inositol 1,2,3,4,6-pentakisphosphate; AICAR, 5-aminoimidazole-4-carboxamide ribonucleoside; AMPK, AMP-activated protein kinase; DIPP, diphosphoinositol polyphosphate phosphohydrolases; HGNC, Human Genome Organization Gene Nomenclature Committee; HPLC, high-performance liquid chromatography; Ins(1,3,4,5)P4, d-myo-inositol 1,3,4,5-tetrakisphosphate; Ins(1,4,5)P3, d-myo-inositol 1,4,5-trisphosphate; InsP5, inositol pentakisphosphate; InsP6, inositol hexakisphosphate; IP6K, inositol hexakisphosphate kinase; MEK, mitogen-activated protein kinase kinase; PD184352, 2-(2-chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide; PD98059, 2′-amino-3′-methoxyflavone; PH, Pleckstrin homology; PLC, phosphoinositide-specific phospholipase C; PP-InsP4, diphosphoinositol tetrakisphosphate; (PP)2-InsP4, bis-diphosphoinositol tetrakisphosphate (“InsP8”); PP-InsP5, diphosphoinositol pentakisphosphate (“InsP7”); PPIP5K, PP-InsP5 kinase; PPP-InsP5, triphosphoinositol pentakisphosphate; TNP, N2-(m-trifluoromethyl)benzyl),N6-(P-nitrobenzyl)purine; U0126, 1,4-diamino-2,3-dicyano-1,4-bis(methylthio)butadiene.

    • Accepted May 12, 2009.
    • Received March 1, 2009.
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  1. Published online before print May 13, 2009, doi: 10.1124/mol.109.055897 Molecular Pharmacology August 2009 vol. 76 no. 2 236-252
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