Host cell protein tyrosine kinases are activated during the entry of Listeria monocytogenes. Possible role of pp60c-src family protein kinases.
Listeria monocytogenes is able to invade a wide range of cell types by inducing its own internalization. Little is known, however, about the host cell proteins affecting the entry process which involves triggering the host cell signal transduction mechanism. We report here that entry of L. monocytogenes strains (serotypes 4b and 1/2a) into Caco-2 cells induced tyrosine phosphorylation of several host cell proteins including pp60c-src substrates. Using specific synthetic peptide substrates, we showed that L. monocytogenes activates, as early as 5 min after bacteria-cell contact, the pp60c-src family-related (srcFR) proteins by an inlAB-dependent pathway. The activation of srcFR proteins seems to be crucial in the entry of L. monocytogenes into Caco-2 cells. Indeed, specific inhibition of the srcFR signal by herbimycin A blocked the entry of L. monocytogenes strains. Taken together, our data show that L. monocytogenes enhances cell tyrosine phosphorylations and activates the pp60c-src family-related proteins by an inlAB-dependent pathway.
Van Langendonck
N
N
Institut National de la Recherche Agronomique, Centre de Tours-Nouzilly, Laboratoire de Pathologie Infectieuse et Immunologie, France.
Velge
P
P
Bottreau
E
E
D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D016227:Benzoquinones; D018938:Caco-2 Cells / Q000201:enzymology / Q000382:microbiology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D047029:Lactams, Macrocyclic; D008089:Listeria monocytogenes / Q000472:pathogenicity*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D009154:Mutation; D010455:Peptides / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000502:physiology
D001426:Bacterial Proteins; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D008565:Membrane Proteins; D010455:Peptides; D011809:Quinones; C095768:inlB protein, Listeria monocytogenes; C069761:internalin protein, Bacteria; D017828:Rifabutin; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src)