PtdIns(5)P activates the host cell PI3-kinase/Akt pathway during Shigella flexneri infection Academic Article uri icon


MeSH Major

  • Bacterial Proteins
  • Phosphatidylinositol 3-Kinases
  • Phosphatidylinositol Phosphates
  • Phosphoric Monoester Hydrolases
  • Proto-Oncogene Proteins c-akt
  • Shigella flexneri
  • Signal Transduction


  • The virulence factor IpgD, delivered into nonphagocytic cells by the type III secretion system of the pathogen Shigella flexneri, is a phosphoinositide 4-phosphatase generating phosphatidylinositol 5 monophosphate (PtdIns5P). We show that PtdIns5P is rapidly produced and concentrated at the entry foci of the bacteria, where it colocalises with phosphorylated Akt during the first steps of infection. Moreover, S. flexneri-induced phosphorylation of host cell Akt and its targets specifically requires IpgD. Ectopic expression of IpgD in various cell types, but not of its inactive mutant, or addition of short-chain penetrating PtdIns5P is sufficient to induce Akt phosphorylation. Conversely, sequestration of PtdIns5P or reduction of its level strongly decreases Akt phosphorylation in infected cells or in IpgD-expressing cells. Accordingly, IpgD and PtdIns5P production specifically activates a class IA PI 3-kinase via a mechanism involving tyrosine phosphorylations. Thus, S. flexneri parasitism is shedding light onto a new mechanism of PI 3-kinase/Akt activation via PtdIns5P production that plays an important role in host cell responses such as survival.

publication date

  • March 8, 2006



  • Academic Article



  • eng

PubMed Central ID

  • PMC1409730

Digital Object Identifier (DOI)

  • 10.1038/sj.emboj.7601001

PubMed ID

  • 16482216

Additional Document Info

start page

  • 1024

end page

  • 34


  • 25


  • 5