Ins(1,4,5)P3 3-kinase-A overexpression induces cytoskeletal reorganization via a kinase-independent mechanism

Biochem J. 2008 Sep 15;414(3):407-17. doi: 10.1042/BJ20080630.


In the present study, effects of increased IP3K-A [Ins(1,4,5)P(3) 3-kinase-A] expression were analysed. H1299 cells overexpressing IP3K-A formed branching protrusions, and under three-dimensional culture conditions, they exhibited a motile fibroblast-like morphology. They lost the ability to form actin stress fibres and showed increased invasive migration in vitro. Furthermore, expression levels of the mesenchymal marker proteins vimentin and N-cadherin were increased. The enzymatic function of IP3K-A is to phosphorylate the calcium-mobilizing second messenger Ins(1,4,5)P(3) to (Ins(1,3,4,5)P(4). Accordingly, cells overexpressing IP3K-A showed reduced calcium release and altered concentrations of InsPs, with decreasing concentrations of Ins(1,4,5)P(3), InsP(6) and Ins(1,2,3,4,5)P(5), and increasing concentrations of Ins(1,3,4,5)P(4). However, IP3K-A-induced effects on cell morphology do not seem to be dependent on enzyme activity, since a protein devoid of enzyme activity also induced the formation of branching protrusions. Therefore we propose that the morphological changes induced by IP3K-A are mediated by non-enzymatic activities of the protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Cytoskeleton / metabolism*
  • Cytoskeleton / ultrastructure
  • Gene Expression
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Inositol Phosphates / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Mutation
  • Phenotype
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Signal Transduction


  • Inositol Phosphates
  • inositol-1,3,4,5-tetrakisphosphate
  • Green Fluorescent Proteins
  • Phosphotransferases (Alcohol Group Acceptor)
  • Inositol 1,4,5-trisphosphate 3-kinase
  • Calcium