c-Src/Lyn kinases activate Helicobacter pylori CagA through tyrosine phosphorylation of the EPIYA motifs
c-Src/Lyn kinases activate Helicobacter pylori CagA through tyrosine phosphorylation of the EPIYA motifs
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DOI：
10.1046/j.1365-2958.2002.02781.x
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发表时间：
2002-02-01
影响因子：
3.6
通讯作者：
Covacci, A
中科院分区：
文献类型：
--
作者：
Stein, M;Bagnoli, F;Covacci, A
人类病原体幽门螺杆菌定植在胃的粘膜层。在寄生虫感染期间，自由游动的细菌粘附于胃上皮细胞并触发细胞内信号传导途径。该过程需要效应蛋白CagA通过cag致病岛中编码的专门的IV型分泌系统易位到宿主细胞中。转移后，CagA在酪氨酸残基上被宿主细胞激酶磷酸化。在这里，我们描述了CagA的酪氨酸磷酸化是如何被限制到一个以前确定的重复序列称为D1。该序列位于蛋白质的C-末端一半，包含5个氨基酸基序EPIYA，其在大部分临床分离株中通过重复扩增。CagA的酪氨酸磷酸化对于导致培养物中生长的细胞形态发生显著变化的活化过程是必不可少的。此外，我们观察到src激酶家族的两个成员，c-Src和林恩，占大多数的CagA特异性激酶活性在宿主细胞裂解物。因此，CagA易位后，在EPIYA基序酪氨酸磷酸化促进生长因子样反应与强烈的细胞骨架重排，细胞伸长效应和细胞运动性增加。
The human pathogen Helicobacter pylori colonizes the mucous layer of the stomach. During parasitic infection, freely swimming bacteria adhere to the gastric epithelial cells and trigger intracellular signalling pathways. This process requires the translocation of the effector protein CagA into the host cell through a specialized type IV secretion system encoded in the cag pathogenicity island. Following transfer, CagA is phosphorylated on tyrosine residues by a host cell kinase. Here, we describe how the tyrosine phosphorylation of CagA is restricted to a previously identified repeated sequence called D1. This sequence is located in the C-terminal half of the protein and contains the five-amino-acid motif EPIYA, which is amplified by duplications in a large fraction of clinical isolates. Tyrosine phosphorylation of CagA is essential for the activation process that leads to dramatic changes in the morphology of cells growing in culture. In addition, we observed that two members of the src kinases family, c-Src and Lyn, account for most of the CagA-specific kinase activity in host cell lysates. Thus, CagA translocation followed by tyrosine phosphorylation at the EPIYA motifs promotes a growth factor-like response with intense cytoskeletal rearrangements, cell elongation effects and increased cellular motility.