Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

Inositol hexakisphosphate kinase 1 regulates neutrophil function in innate immunity by inhibiting phosphatidylinositol-(3,4,5)-trisphosphate signaling

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Prasad, A.
  • Jia, Y.
  • Chakraborty, Anutosh
  • Li, Y.
  • Jain, S. K.
  • Zhong, J.
  • Roy, S. G.
  • Loison, F.
  • Mondal, S.
  • Sakai, J.
  • Blanchard, C.
  • Snyder, S. H.
  • Luo, H. R.

publication date

  • August 2011

journal

  • Nature Immunology  Journal

abstract

  • Inositol 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)P3)-mediated membrane translocation of the pleckstrin homology domain of the kinase Akt and thus augmented downstream PtdIns(3,4,5)P3 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)P3-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)P3 signaling in neutrophils.

subject areas

  • Animals
  • Dimethyl Sulfoxide
  • HL-60 Cells
  • Humans
  • Immunity, Innate
  • Inositol Phosphates
  • Isoenzymes
  • Mice
  • Mice, Knockout
  • N-Formylmethionine Leucyl-Phenylalanine
  • Neutrophils
  • Phagocytosis
  • Phosphatidylinositol Phosphates
  • Phosphotransferases (Phosphate Group Acceptor)
  • Proto-Oncogene Proteins c-akt
  • RNA
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
scroll to property group menus

Identity

PubMed Central ID

  • PMC3140608

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/ni.2052

PubMed ID

  • 21685907
scroll to property group menus

Additional Document Info

start page

  • 752

end page

  • 760

volume

  • 12

issue

  • 8

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support