The Listeria monocytogenes protein InlB is an agonist of mammalian phosphoinositide 3-kinase

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 In1B, Here we investigate the role of In1B in regulating mammalian signal transduction and cytoskeletal structure. Treatment of Vero cells with purified In1B caused rapid and transient increases in the lipid products of the PI 3-kinase p85-p110, tyrosine phosphorylation of the mammalian adaptor proteins Gab1, Chi, and Shc, and association of these proteins with p85. In1B also stimulated large scale changes in the actin cytoskeleton(membrane ruffling), which were PIS-kinase-dependent. These results identify In1B 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.