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 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.
Ireton
K
K
Unité des Interactions Bactéries-Cellules, 28 rue du Dr. Roux, Institut Pasteur, 75724 Paris, Cedex 15, France. k.ireton@utoronto.ca
Payrastre
B
B
Cossart
P
P
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000648:ultrastructure; D002522:Chlorocebus aethiops; D003599:Cytoskeleton; D066246:ErbB Receptors / Q000378:metabolism; D008089:Listeria monocytogenes / Q000472:pathogenicity*; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000032:analysis; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases; D014709:Vero Cells
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D001426:Bacterial Proteins; D002352:Carrier Proteins; D066246:ErbB Receptors; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D010716:Phosphatidylinositols; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050721:Proto-Oncogene Proteins c-cbl; D055765:Shc Signaling Adaptor Proteins; D044767:Ubiquitin-Protein Ligases; C095768:inlB protein, Listeria monocytogenes; C067419:CBL protein, human