Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

PPIP5K

  • Stephen B. Shears
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101515

Synonyms

 Asp1;  VIH;  Vip1

Historical Background

PPIP5Ks (E.C. 2.7.4.24) are ATP-dependent, small molecule kinases that synthesize inositol pyrophosphates (PP-InsPs), which are intracellular signals with functionally significant and “energetic” phosphoanhydride bonds. The purification and cloning of these enzymes was first described in a body of work that was performed independently by two groups and published in 2007 (Choi et al. 2007; Fridy et al. 2007; Mulugu et al. 2007). PPIP5Ks are distributed throughout eukaryotic kingdoms; the orthologs have aliases: Asp1 in Schizosaccharomyces pombe, Vip1 in Saccharomyces cerevisiae, VIH in Arabidopsis thaliana. Since yeasts and plants diverged from the animal kingdom 1.3 and 1.5 billion years ago, respectively (see www.timetree.org), it is clear that PPIP5Ks are evolutionarily ancient enzymes. Two PPIP5K genes are expressed in both mammals and plants (Choi et al. 2007; Fridy et al. 2007; Laha et al. 2015; Mulugu et al. 2007).

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References

  1. Chakraborty A, Koldobskiy MA, Bello NT, Maxwell M, Potter JJ, Juluri KR, et al. Inositol pyrophosphates inhibit akt signaling, thereby regulating insulin sensitivity and weight gain. Cell. 2010;143:897–910.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Choi JH, Williams J, Cho J, Falck JR, Shears SB. Purification, sequencing, and molecular identification of a mammalian PP-InsP5 kinase that is activated when cells are exposed to hyperosmotic stress. J Biol Chem. 2007;282:30763–75.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Choi K, Mollapour E, Choi JH, Shears SB. Cellular energetic status supervises the synthesis of bis-diphosphoinositol tetrakisphosphate independently of AMP-activated protein kinase. Mol Pharmacol. 2008;74:527–36.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Fridy PC, Otto JC, Dollins DE, York JD. Cloning and characterization of two human VIP1-like inositol hexakisphosphate and diphosphoinositol pentakisphosphate kinases. J Biol Chem. 2007;282:30754–62.CrossRefPubMedGoogle Scholar
  5. Gokhale NA, Zaremba A, Janoshazi AK, Weaver JD, Shears SB. PPIP5K1 modulates ligand competition between diphosphoinositol polyphosphates and PtdIns(3,4,5)P3 for polyphosphoinositide-binding domains. Biochem J. 2013;453:413–26.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Gokhale NA, Zaremba A, Shears SB. Receptor-dependent compartmentalization of PPIP5K1, a kinase with a cryptic polyphosphoinositide binding domain. Biochem J. 2011;434:415–26.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Laha D, Johnen P, Azevedo C, Dynowski M, Weiss M, Capolicchio S, et al. VIH2 regulates the synthesis of inositol pyrophosphate InsP8 and jasmonate-dependent defenses in arabidopsis. Plant Cell. 2015;27:1082–97.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Lee YS, Mulugu S, York JD, O'Shea EK. Regulation of a cyclin-CDK-CDK inhibitor complex by inositol pyrophosphates. Science. 2007;316:109–12.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Machkalyan G, Trieu P, Petrin D, Hebert TE, Miller GJ. PPIP5K1 interacts with the exocyst complex through a C-terminal intrinsically disordered domain and regulates cell motility. Cell Signal. 2016;28:401–11.CrossRefPubMedGoogle Scholar
  10. Mulugu S, Bai W, Fridy PC, Bastidas RJ, Otto JC, Dollins DE, et al. A conserved family of enzymes that phosphorylate inositol hexakisphosphate. Science. 2007;316:106–9.CrossRefPubMedGoogle Scholar
  11. Padmanabhan U, Dollins DE, Fridy PC, York JD, Downes CP. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Pohlmann J, Fleig U. Asp1, a conserved 1/3 inositol polyphosphate kinase, regulates the dimorphic switch in S. pombe. Mol Cell Biol. 2010;30:4535–47.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Pohlmann J, Risse C, Seidel C, Pohlmann T, Jakopec V, Walla E, et al. The vip1 inositol polyphosphate kinase family regulates polarized growth and modulates the microtubule cytoskeleton in fungi. PLoS Genet. 2014;10:e1004586.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Pulloor NK, Nair S, Kostic AD, Bist P, Weaver JD, Tyagi R, et al. Human genome-wide RNAi screen identifies an essential role for inositol pyrophosphates in type-I interferon response. PLoS Pathog. 2014;10:e1003981.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Thota SG, Bhandari R. The emerging roles of inositol pyrophosphates in eukaryotic cell physiology. J Biosci. 2015;40:593–605.CrossRefPubMedGoogle Scholar
  16. Wang H, Falck JR, Hall TM, Shears SB. Structural basis for an inositol pyrophosphate kinase surmounting phosphate crowding. Nat Chem Biol. 2012;8:111–6.CrossRefGoogle Scholar
  17. Wang H, Godage HY, Riley AM, Weaver JD, Shears SB, Potter BVL. Synthetic inositol phosphate analogs reveal that PPIP5K2 has a surface-mounted substrate capture site that is a target for drug discovery. Chem Biol. 2014;21:689–99.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Wang H, Nair VS, Holland AA, Capolicchio S, Jessen HJ, Johnson MK, et al. Asp1 from Schizosaccharomyces pombe binds a [2Fe-2S](2+) cluster which inhibits inositol pyrophosphate 1-phosphatase activity. Biochemistry. 2015;54:6462–74.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Weaver JD, Wang H, Shears SB. The kinetic properties of a human PPIP5K reveal that its kinase activities are protected against the consequences of a deteriorating cellular bioenergetic environment. Biosci Rep. 2013;33:228–41.CrossRefGoogle Scholar
  20. Yong ST, Nguyen HN, Choi JH, Bortner CD, Williams J, Pulloor NK, et al. Identification of a functional nuclear translocation sequence in hPPIP5K2. BMC Cell Biol. 2015;16:17.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Laboratory of Signal Transduction, Inositol Signaling SectionNational Institute of Environmental Health Sciences, National Institutes of HealthResearch Triangle ParkUSA