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Sci. Signal., 20 September 2011
Vol. 4, Issue 191, p. ra61
[DOI: 10.1126/scisignal.2001619]

RESEARCH ARTICLES

Editor's Summary

Launching a Lipid Weapon
Dysentery caused by the pathogenic bacterium Shigella flexneri causes considerable mortality, especially among infants in developing nations. S. flexneri injects several proteins into infected host cells, including an enzyme called IpgD that generates PI5P, a lipid that enhances host cell survival through the PI3K-Akt signaling pathway. Ramel et al. found that IpgD-generated PI5P activated the epidermal growth factor receptor (EGFR) and that this lipid prevented the receptor from being trafficked to lysosomes, subcellular compartments in which activated EGFR is broken down. The authors note that other pathogenic bacteria also produce enzymes that generate PI5P, thus raising the possibility that this survival strategy may be conserved and therefore a potential therapeutic target.

Citation: D. Ramel, F. Lagarrigue, V. Pons, J. Mounier, S. Dupuis-Coronas, G. Chicanne, P. J. Sansonetti, F. Gaits-Iacovoni, H. Tronchère, B. Payrastre, Shigella flexneri Infection Generates the Lipid PI5P to Alter Endocytosis and Prevent Termination of EGFR Signaling. Sci. Signal. 4, ra61 (2011).

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Systems-Level Overview of Host Protein Phosphorylation During Shigella flexneri Infection Revealed by Phosphoproteomics.
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Mol. Cell. Proteomics 12, 2952-2968
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Lipid Sorting and Multivesicular Endosome Biogenesis.
C. Bissig and J. Gruenberg (2013)
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Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation.
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PtdIns5P is an oxidative stress-induced second messenger that regulates PKB activation.
D. R. Jones, R. Foulger, W.-J. Keune, Y. Bultsma, and N. Divecha (2013)
FASEB J 27, 1644-1656
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Production of phosphatidylinositol 5-phosphate via PIKfyve and MTMR3 regulates cell migration.
A. Oppelt, V. H. Lobert, K. Haglund, A. M. Mackey, L. E. Rameh, K. Liestol, K. Oliver Schink, N. Marie Pedersen, E. M. Wenzel, E. M. Haugsten, et al. (2013)
EMBO Rep. 14, 57-64
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In vivo, Pikfyve generates PI(3,5)P2, which serves as both a signaling lipid and the major precursor for PI5P.
S. N. Zolov, D. Bridges, Y. Zhang, W.-W. Lee, E. Riehle, R. Verma, G. M. Lenk, K. Converso-Baran, T. Weide, R. L. Albin, et al. (2012)
PNAS 109, 17472-17477
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