Research ArticleHost-Pathogen Interactions

Shigella flexneri Infection Generates the Lipid PI5P to Alter Endocytosis and Prevent Termination of EGFR Signaling

See allHide authors and affiliations

Science Signaling  20 Sep 2011:
Vol. 4, Issue 191, pp. ra61
DOI: 10.1126/scisignal.2001619

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution


The phosphoinositide metabolic pathway, which regulates cellular processes implicated in survival, motility, and trafficking, is often subverted by bacterial pathogens. Shigella flexneri, a bacterium that causes dysentery, injects IpgD, a phosphoinositide phosphatase that generates the lipid phosphatidylinositol 5-phosphate (PI5P), into host cells, thereby activating the phosphoinositide 3-kinase–Akt survival pathway. We show that epidermal growth factor receptor (EGFR) is required for PI5P-dependent activation of Akt in infected HeLa cells or cells ectopically expressing IpgD. Cells treated with PI5P had increased numbers of early endosomes with activated EGFR, no detectable EGFR in the late endosomal or lysosomal compartments, and prolonged EGFR signaling. Endosomal recycling and retrograde pathways were spared, indicating that the effect of PI5P on the degradative route to the late endocytic compartments was specific. Thus, we identified PI5P, which was enriched in endosomes, as a regulator of vesicular trafficking that alters growth factor receptor signaling by impairing lysosomal degradation, a property used by S. flexneri to favor survival of host cells.

View Full Text

Stay Connected to Science Signaling

Editor's Blog