PtdIns5P protects Akt from dephosphorylation through PP2A inhibition.
Phosphatidylinositol 5-phosphate (PtdIns5P), the most recently discovered phosphoinositide, has been proposed to play a role as a lipid mediator of intracellular signaling. We have previously shown that PtdIns5P generated by IpgD, an effector of the causative agent of dysentery Shigella flexneri, activates the PI 3-kinase/Akt pathway. Here, we demonstrate that PtdIns5P is able to protect Akt from dephosphorylation. This effect is not due to inhibition of the phosphoinositide phosphatase regulating PtdIns(3,4,5)P(3) levels PTEN but rather to PtdIns5P-induced phosphorylation and subsequent inhibition of the catalytic subunit of PP2A phosphatases. These data shed light on a new mechanism used by S. flexneri bacteria to sustain Akt activation to increase survival of the host cells during bacterial replication.
Ramel
Damien
D
INSERM U563, Toulouse, France. damien.ramel@inserm.fr
Lagarrigue
Frédéric
F
Dupuis-Coronas
Sophie
S
Chicanne
Gaëtan
G
Leslie
Nicholas
N
Gaits-Iacovoni
Frédérique
F
Payrastre
Bernard
B
Tronchère
Hélène
H
D006367:HeLa Cells; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012763:Shigella flexneri / Q000378:metabolism
D018129:Phosphatidylinositol Phosphates; C113567:phosphatidylinositol 5-phosphate; D051057:Proto-Oncogene Proteins c-akt; D054648:Protein Phosphatase 2; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human