title: The invasion protein InIB from Listeria monocytogenes activates PLC-gamma1 downstream from PI 3-kinase.
abstract: Entry of the bacterial pathogen Listeria monocytogenes into non-phagocytic mammalian cells is mainly mediated by the InlB protein. Here we show that in the human epithelial cell line HEp-2, the invasion protein InlB activates sequentially a p85beta-p110 class I(A) PI 3-kinase and the phospholipase C-gamma1 (PLC-gamma1) without detectable tyrosine phosphorylation of PLC-gamma1. Purified InlB stimulates association of PLC-gamma1 with one or more tyrosine-phosphorylated proteins, followed by a transient increase in intracellular inositol 1,4,5-trisphosphate (IP3) levels and a release of intracellular Ca2+ in a PI 3-kinase-dependent manner. Infection of HEp-2 cells with wild-type L. monocytogenes bacteria also induces association of PLC-gamma1 with phosphotyrosyl proteins. This interaction is undetectable upon infection with a deltainlB mutant revealing an InlB specific signal. Interestingly, pharmacological or genetic inactivation of PLC-gamma1 does not significantly affect InlB-mediated bacterial uptake, suggesting that InlB-mediated PLC-gamma1 activation and calcium mobilization are involved in post-internalization steps.
authors.affiliation: Unité des Interactions Bactéries-Cellules, Institut Pasteur, Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Bierne
authors.forename: S
authors.initials: S
authors.lastname: Dramsi
authors.forename: M P
authors.initials: MP
authors.lastname: Gratacap
authors.forename: C
authors.initials: C
authors.lastname: Randriamampita
authors.forename: G
authors.initials: G
authors.lastname: Carpenter
authors.forename: B
authors.initials: B
authors.lastname: Payrastre
authors.forename: P
authors.initials: P
authors.lastname: Cossart
mesh_terms: D001426:Bacterial Proteins; D002118:Calcium / Q000378:metabolism; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000382:microbiology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000472:pathogenicity* / Q000502:physiology; D008088:Listeriosis / Q000382:microbiology*; D008565:Membrane Proteins / Q000378:metabolism / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051966:Phospholipase C gamma; D010766:Phosphorylation; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; C095768:inlB protein, Listeria monocytogenes; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium