The amoebal MAP kinase response to Legionella pneumophila is regulated by DupA.

The amoebal MAP kinase response to Legionella pneumophila is regulated by DupA.
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DOI:
10.1016/j.chom.2009.08.005
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发表时间:
2009-09-17
影响因子:
30.3
通讯作者:
Isberg RR
Isberg RR
中科院分区:
医学1区
文献类型:
--
作者:
Li Z;Dugan AS;Bloomfield G;Skelton J;Ivens A;Losick V;Isberg RR

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dupA基因,编码一个假定的酪氨酸激酶/双特异性磷酸酶(Dusp),被确定在一个屏幕中的Dictyosteobacteriumdiscoideum突变体改变支持嗜肺军团菌细胞内复制。dupA的缺乏导致ERK 1的过度磷酸化,与磷酸酶活性的丧失以及ERK 2的降解一致。ERK 1的过度磷酸化模拟了野生型阿米巴原虫细菌攻击后这种蛋白质的反应。与高等真核细胞中的Dusps类似,阿米巴dupA基因在细菌接触后被诱导,表明Dusps的反应是从阿米巴到哺乳动物的保守反应。在dupA−突变体中,大量基因被错误调控,这些基因与对L.嗜肺菌感染一些阿米巴基因似乎参与了类似于高等真核生物先天免疫的反应,表明对细菌的保守反应存在失调。
The dupA gene, encoding a putative tyrosine kinase/dual specificity phosphatase (Dusp), was identified in a screen for Dictyostelium discoideum mutants altered in supporting Legionella pneumophila intracellular replication. The absence of dupA resulted in hyperphosphorylation of ERK1, consistent with the loss of a phosphatase activity, as well as degradation of ERK2. ERK1 hyperphosphorylation mimicked the response of this protein after bacterial challenge of wild type amoebae. Similar to Dusps in higher eukaryotic cells, the amoebal dupA gene was induced after bacterial contact, indicating a response of Dusps that is conserved from amoebae to mammals. A large set of genes was misregulated in the dupA− mutant that largely overlaps with genes responding to L. pneumophila infection. Some of the amoebal genes appear to be involved in a response similar to innate immunity in higher eukaryotes, indicating there was misregulation of a conserved response to bacteria.
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