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The Phosphoinositol-3-Kinase–Protein Kinase B/Akt Pathway Is Critical forPseudomonas aeruginosaStrain PAK Internalization
- Source :
- Molecular Biology of the Cell. 16:2577-2585
- Publication Year :
- 2005
- Publisher :
- American Society for Cell Biology (ASCB), 2005.
-
Abstract
- Several Pseudomonas aeruginosa strains are internalized by epithelial cells in vitro and in vivo, but the host pathways usurped by the bacteria to enter nonphagocytic cells are not clearly understood. Here, we report that internalization of strain PAK into epithelial cells triggers and requires activation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B/Akt (Akt). Incubation of Madin-Darby canine kidney (MDCK) or HeLa cells with the PI3K inhibitors LY294002 (LY) or wortmannin abrogated PAK uptake. Addition of the PI3K product phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] to polarized MDCK cells was sufficient to increase PAK internalization. PtdIns(3,4,5)P3accumulated at the site of bacterial binding in an LY-dependent manner. Akt phosphorylation correlated with PAK invasion. The specific Akt phosphorylation inhibitor SH-5 inhibited PAK uptake; internalization also was inhibited by small interfering RNA-mediated depletion of Akt phosphorylation. Expression of constitutively active Akt was sufficient to restore invasion when PI3K signaling was inhibited. Together, these results demonstrate that the PI3K signaling pathway is necessary and sufficient for the P. aeruginosa entry and provide the first example of a bacterium that requires Akt for uptake into epithelial cells.
- Subjects :
- media_common.quotation_subject
macromolecular substances
Protein Serine-Threonine Kinases
Biology
Cell Line
Wortmannin
Phosphatidylinositol 3-Kinases
chemistry.chemical_compound
Dogs
Phosphatidylinositol Phosphates
Proto-Oncogene Proteins
Animals
Humans
LY294002
Phosphatidylinositol
RNA, Small Interfering
Internalization
Molecular Biology
Protein kinase B
PI3K/AKT/mTOR pathway
media_common
Kinase
Epithelial Cells
Articles
Cell Biology
Molecular biology
Cell biology
Enzyme Activation
chemistry
Pseudomonas aeruginosa
Signal transduction
Proto-Oncogene Proteins c-akt
HeLa Cells
Signal Transduction
Subjects
Details
- ISSN :
- 19394586 and 10591524
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Molecular Biology of the Cell
- Accession number :
- edsair.doi.dedup.....d23d689112eed924f852d9676926221b