Skip to main content

PPIP5K

  • Living reference work entry
  • First Online:
Encyclopedia of Signaling Molecules
  • 211 Accesses

Synonyms

Vip1; Asp1; VIH

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).

The Biological...

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • Thota SG, Bhandari R. The emerging roles of inositol pyrophosphates in eukaryotic cell physiology. J Biosci. 2015;40:593–605.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stephen B. Shears .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media LLC

About this entry

Cite this entry

Shears, S.B. (2016). PPIP5K. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_101515-1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-6438-9_101515-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-6438-9

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics