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dc.contributor.authorPrasad, Amit
dc.contributor.authorJia, Yonghui
dc.contributor.authorChakraborty, Anutosh
dc.contributor.authorLi, Yitang
dc.contributor.authorJain, Supriya K.
dc.contributor.authorZhong, Jia
dc.contributor.authorRoy, Saurabh Ghosh
dc.contributor.authorLoison, Fabien
dc.contributor.authorMondal, Subhanjan
dc.contributor.authorSakai, Jiro
dc.contributor.authorBlanchard, Catlyn
dc.contributor.authorSnyder, Solomon H.
dc.contributor.authorLuo, Hongbo
dc.date.accessioned2014-11-05T18:16:29Z
dc.date.issued2011
dc.identifier.citationPrasad, Amit, Yonghui Jia, Anutosh Chakraborty, Yitang Li, Supriya K. Jain, Jia Zhong, Saurabh Ghosh Roy, et al. 2011. “Inositol Hexakisphosphate Kinase 1 Regulates Neutrophil Function in Innate Immunity by Inhibiting Phosphatidylinositol-(3,4,5)-Trisphosphate Signaling.” Nature Immunology 12 (8) (June 19): 752–760. doi:10.1038/ni.2052. http://dx.doi.org/10.1038/ni.2052.en_US
dc.identifier.issn1529-2908en_US
dc.identifier.issn1529-2916en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13350203
dc.description.abstractInositol phosphates are widely produced throughout animal and plant tissues. Diphosphoinositol pentakisphosphate (InsP7) contains an energetic pyrophosphate bond. Here we demonstrate that disruption of inositol hexakisphosphate kinase 1 (InsP6K1), one of the three mammalian inositol hexakisphosphate kinases (InsP6Ks) that convert inositol hexakisphosphate (InsP6) to InsP7, conferred enhanced phosphatidylinositol-(3,4,5)-trisphosphate \((PtdIns(3,4,5)P_3)\)-mediated membrane translocation of the pleckstrin homology domain of the kinase Akt and thus augmented downstream \(PtdIns(3,4,5)P_3\) signaling in mouse neutrophils. Consequently, these neutrophils had greater phagocytic and bactericidal ability and amplified NADPH oxidase–mediated production of superoxide. These phenotypes were replicated in human primary neutrophils with pharmacologically inhibited InsP6Ks. In contrast, an increase in intracellular InsP7 blocked chemoattractant-elicited translocation of the pleckstrin homology domain to the membrane and substantially suppressed \(PtdIns(3,4,5)P_3\)-mediated cellular events in neutrophils. Our findings establish a role for InsP7 in signal transduction and provide a mechanism for modulating \(PtdIns(3,4,5)P_3\) signaling in neutrophils.en_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofdoi:10.1038/ni.2052en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pubmed/21685907en_US
dash.licenseMETA_ONLY
dc.titleInositol Hexakisphosphate Kinase 1 Regulates Neutrophil Function in Innate Immunity by Inhibiting Phosphatidylinositol-(3,4,5)-Trisphosphate Signalingen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalNature Immunologyen_US
dash.depositing.authorLuo, Hongbo
dash.embargo.until10000-01-01
dc.identifier.doi10.1038/ni.2052*
workflow.legacycommentsDeposit dark per Luoen_US
dash.authorsorderedfalse
dash.contributor.affiliatedLoison, Fabien
dash.contributor.affiliatedLuo, Hongbo


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