title: The amoebal MAP kinase response to Legionella pneumophila is regulated by DupA.
abstract: The amoeba Dictyostelium discoideum can support replication of Legionella pneumophila. Here we identify the dupA gene, encoding a putative tyrosine kinase/dual-specificity phosphatase, in a screen for D. discoideum mutants altered in allowing L. pneumophila intracellular replication. Inactivation of dupA resulted in depressed L. pneumophila growth and sustained hyperphosphorylation of the amoebal MAP kinase ERK1, consistent with loss of a phosphatase activity. Bacterial challenge of wild-type amoebae induced dupA expression and resulted in transiently increased ERK1 phosphorylation, suggesting that dupA and ERK1 are part of a response to bacteria. Indeed, over 500 of the genes misregulated in the dupA(-) mutant were regulated in response to L. pneumophila infection, including some thought to have immune-like functions. MAP kinase phosphatases are known to be highly upregulated in macrophages challenged with L. pneumophila. Thus, DupA may regulate a MAP kinase response to bacteria that is conserved from amoebae to mammals.
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Zhiru
authors.initials: Z
authors.lastname: Li
authors.forename: Aisling S
authors.initials: AS
authors.lastname: Dugan
authors.forename: Gareth
authors.initials: G
authors.lastname: Bloomfield
authors.forename: Jason
authors.initials: J
authors.lastname: Skelton
authors.forename: Alasdair
authors.initials: A
authors.lastname: Ivens
authors.forename: Vicki
authors.initials: V
authors.lastname: Losick
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Isberg
mesh_terms: D000818:Animals; D004023:Dictyostelium / Q000201:enzymology* / Q000235:genetics / Q000382:microbiology*; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D016952:Legionella pneumophila / Q000254:growth & development*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D011505:Protein-Tyrosine Kinases; D048052:Mitogen-Activated Protein Kinase 3; D010744:Phosphoric Monoester Hydrolases