Listeria monocytogenes invasion of epithelial cells requires the MEK-1/ERK-2 mitogen-activated protein kinase pathway
Listeria monocytogenes invasion of epithelial cells requires the MEK-1/ERK-2 mitogen-activated protein kinase pathway
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DOI：
10.1128/iai.66.3.1106-1112.1998
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发表时间：
1998-03-01
影响因子：
3.1
通讯作者：
Finlay, BB
中科院分区：
文献类型：
--
作者：
Tang, P;Sutherland, CL;Finlay, BB
MEK-1丝裂原活化蛋白激酶（MAPK-1 mitogen-activated protein kinase kinase，MAP）的特异性抑制剂PD 98059可阻断单核细胞增生李斯特菌（Listeria monocytogenes）对HeLa上皮细胞的侵袭。PD 98059的作用是可逆的，因为去除药物后粘附的细胞外细菌仅仅内化。此前，我们报道了L。单核细胞增多症可以通过溶血素O（LLO）对宿主细胞的作用激活ERK-1和ERK-2 MAP激酶（P. Tang，I. Rosenshine，P. Cossart，and B. B。芬利感染Immun. 64：2359-2361，1996）。我们现在已经发现，另外两个MAP激酶途径，即p38 MAP激酶和c-Jun N-末端激酶，也被野生型L.单核细胞增多症缺乏功能性LLO的突变体（hly突变体）仍然具有侵袭性，但仅激活ERK-2，并且仅在感染后90分钟激活。两种L.单核细胞增多症侵袭，细胞松弛素D，破坏肌动蛋白聚合，渥曼青霉素，阻断磷脂酰肌醇（TI）3-激酶活性，没有阻断ERK-2激活。单核细胞增多症和hly突变体。Ho il-ever、酪氨酸激酶抑制剂金雀异黄素和PD 98059都可以阻断侵袭并降低ERK-2的激活。这些结果表明，MEK-1和ERK-2活性是必不可少的L。单核细胞增多症侵入宿主上皮细胞。这是第一个报告表明MAP激酶途径是细菌入侵所必需的。
PD98059, a specific inhibitor of MEK-1 mitogen-activated protein (MAP) kinase kinase, blocked Listeria monocytogenes invasion into HeLa epithelial cells. The effects of PD98059 were reversible, as adherent extracellular bacteria mere internalized upon removal of the drug. Previously, we reported that L. monocytogenes could activate ERK-1 and ERK-2 MAP kinases through the action of listeriolysin O (LLO) on the host cell (P. Tang, I. Rosenshine, P. Cossart, and B. B. Finlay, Infect. Immun. 64:2359-2361, 1996). We have now found that two other MAP kinase pathways, those of p38 MAP kinase and c-Jun N-terminal kinase, are also activated by wildtype L. monocytogenes. Mutants lacking functional LLO (hly mutants) were still invasive but only activated ERK-2 and only activated it at later (90-min) postinfection times. Two inhibitors of L. monocytogenes invasion, cytochalasin D, which disrupts actin polymerization, and wortmannin, which blocks phosphatidylinositol (TI) 3-kinase activity, did not block ERK-2 activation bg wild-type L. monocytogenes and hly mutants. Ho il-ever, genistein, an inhibitor of tyrosine kinases, and PD98059 both blocked invasion and decreased ERK-2 activation. These results suggest that MEK-1 and ERK-2 activities are essential for L. monocytogenes invasion into host epithelial cells. This is the first report to Show that a MAP kinase pathway is required for bacterial invasion.