The Listeria monocytogenes Protein InlB Is an Agonist of Mammalian Phosphoinositide 3-Kinase

Keith Ireton,Bernard Payrastre,Pascale Cossart

doi:10.1074/jbc.274.24.17025

Keith Ireton, Bernard Payrastre + Show 1 more

Open Access

https://doi.org/10.1074/jbc.274.24.17025

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Abstract

The Gram-positive pathogen Listeria monocytogenes induces its own internalization into some non-phagocytic mammalian cells by stimulating host tyrosine phosphorylation, phosphoinositide (PI) 3-kinase activity, and rearrangements in the actin cytoskeleton. Entry into many cultured cell lines is mediated by the bacterial protein InlB. Here we investigate the role of InlB in regulating mammalian signal transduction and cytoskeletal structure. Treatment of Vero cells with purified InlB caused rapid and transient increases in the lipid products of the PI 3-kinase p85-p110, tyrosine phosphorylation of the mammalian adaptor proteins Gab1, Cbl, and Shc, and association of these proteins with p85. InlB also stimulated large scale changes in the actin cytoskeleton (membrane ruffling), which were PI 3-kinase-dependent. These results identify InlB as the first reported non-mammalian agonist of PI 3-kinase and demonstrate similarities in the signal transduction events elicited by this bacterial protein and known agonists such as epidermal growth factor.

Highlights

Infection of viral, bacterial, or protozoan intracellular pathogens often involves subversion of mammalian signaling pathways
InlB Stimulates PI 3-Kinase Activity in Mammalian Cells—Infection of Vero cells with a bacterial strain deleted for the inlB gene (⌬inlB) results in smaller increases in PtdIns[3,4,5]P3 than is observed upon infection with wt (⌬inlBϩ) L. monocytogenes, indicating that InlB is needed for full activation of p85-p110 [6]
On the basis of these results, it was not known whether InlB itself is an agonist of p85-p110 or whether this bacterial protein only plays an accessory role in PI 3-kinase activation

Summary

Introduction

Bacterial, or protozoan intracellular pathogens often involves subversion of mammalian signaling pathways. InlB Stimulates PI 3-Kinase Activity in Mammalian Cells—Infection of Vero cells with a bacterial strain deleted for the inlB gene (⌬inlB) results in smaller increases in PtdIns[3,4,5]P3 than is observed upon infection with wt (⌬inlBϩ) L. monocytogenes, indicating that InlB is needed for full activation of p85-p110 [6].

Results

Conclusion