Inositol polyphosphate multikinase is a nuclear PI3-kinase with transcriptional regulatory activity

Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12783-8. doi: 10.1073/pnas.0506184102. Epub 2005 Aug 25.

Abstract

Phosphatidylinositol 3,4,5-trisphosphate is a major intracellular messenger molecule thought to be formed almost exclusively by cytosolic, wortmannin-inhibited phosphoinositide 3-kinase family members. Inositol polyphosphate multikinase was identified as an enzyme that generates a series of water-soluble inositol phosphates. We now report the robust, physiologic, and evolutionarily conserved phosphoinositide 3-kinase activity of inositol polyphosphate multikinase, which is localized to nuclei and unaffected by wortmannin. In yeast, this inositol lipid kinase activity physiologically regulates transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Cell Line
  • Cell Nucleus / enzymology*
  • Cell Nucleus / genetics
  • Chlorocebus aethiops
  • Gene Expression Regulation*
  • Humans
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Protein Kinase Inhibitors / pharmacology
  • RNA, Messenger / genetics
  • Rats
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Transaminases / genetics
  • Transaminases / metabolism
  • Transcription, Genetic / genetics*
  • Wortmannin

Substances

  • Androstadienes
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • Transaminases
  • acetylornithine transaminase
  • Phosphotransferases (Alcohol Group Acceptor)
  • inositol polyphosphate multikinase
  • Wortmannin