Abstract |
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.
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Authors | Caroline Pendaries, Hélène Tronchère, Laurence Arbibe, Joelle Mounier, Or Gozani, Lewis Cantley, Michael J Fry, Frédérique Gaits-Iacovoni, Philippe J Sansonetti, Bernard Payrastre |
Journal | The EMBO journal
(EMBO J)
Vol. 25
Issue 5
Pg. 1024-34
(Mar 08 2006)
ISSN: 0261-4189 [Print] England |
PMID | 16482216
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Bacterial Proteins
- Phosphatidylinositol Phosphates
- phosphatidylinositol 5-phosphate
- Tyrosine
- Phosphatidylinositol 3-Kinases
- Proto-Oncogene Proteins c-akt
- IpgD protein, Shigella flexneri
- Phosphoric Monoester Hydrolases
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Topics |
- Animals
- Bacterial Proteins
(genetics, metabolism)
- Cell Survival
(drug effects)
- Cells, Cultured
(drug effects, metabolism, microbiology)
- Fibroblasts
(drug effects, metabolism, microbiology)
- HeLa Cells
- Humans
- Kidney
(drug effects, metabolism, microbiology)
- Mice
- Mice, Knockout
- Mutation
- Phosphatidylinositol 3-Kinases
(metabolism)
- Phosphatidylinositol Phosphates
(metabolism)
- Phosphoric Monoester Hydrolases
(genetics, metabolism)
- Phosphorylation
(drug effects)
- Proto-Oncogene Proteins c-akt
(metabolism)
- Shigella flexneri
(pathogenicity)
- Signal Transduction
- Tyrosine
(metabolism)
- Virulence
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