The Yersinia virulence factor YopM forms a novel protein complex with two cellular kinases
The Yersinia virulence factor YopM forms a novel protein complex with two cellular kinases
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DOI：
10.1074/jbc.m301226200
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发表时间：
2003-05-16
影响因子：
4.8
通讯作者：
Dixon, JE
中科院分区：
文献类型：
--
作者：
McDonald, C;Vacratsis, PO;Dixon, JE
致病性耶尔森氏菌含有毒力质粒，其编码细胞内效应物的基因，所述细胞内效应物中和宿主免疫应答。一种效应子YopM是耶尔森氏菌毒力所必需的，但其在宿主细胞中的功能尚不清楚。为了鉴定受YopM影响的潜在细胞途径，分离并通过质谱鉴定哺乳动物细胞中与YopM共免疫沉淀的蛋白质。结果表明，两种激酶，蛋白激酶C样2（PRK 2）和核糖体S6蛋白激酶1（RSK 1），直接与YopM相互作用。这两种激酶仅在YopM存在时才结合，并且YopM在细胞中的表达刺激这两种激酶的活性。RSK 1通过与YopM的相互作用直接激活，并且RSK 1激酶活性是YopM刺激的PRK 2活性所必需的。RSK1的YopM活化独立于YopJ对MAPK通路的作用而发生。YopM也是耶尔森氏菌诱导的感染巨噬细胞中RSK1迁移率变化所必需的。这些结果鉴定了YopM的第一个细胞内靶点，并表明YopM可刺激PRK 2和RSK 1的活性。
Pathogenic Yersinia contain a virulence plasmid that encodes genes for intracellular effectors, which neutralize the host immune response. One effector, YopM, is necessary for Yersinia virulence, but its function in host cells is unknown. To identify potential cellular pathways affected by YopM, proteins that co-immunoprecipitate with YopM in mammalian cells were isolated and identified by mass spectrometry. Results demonstrate that two kinases, protein kinase C-like 2 (PRK2) and ribosomal S6 protein kinase 1 (RSK1), interact directly with YopM. These two kinases associate only when YopM is present, and expression of YopM in cells stimulates the activity of both kinases. RSK1 is activated directly by interaction with YopM, and RSK1 kinase activity is required for YopM-stimulated PRK2 activity. YopM activation of RSK1 occurs independently of the actions of YopJ on the MAPK pathway. YopM is also required for Yersinia-induced changes in RSK1 mobility in infected macrophage cells. These results identify the first intracellular targets of YopM and suggest YopM acts to stimulate the activity of PRK2 and RSK1.