The CagA protein of Helicobacter pylori is translocated into epithelial cells and binds to SHP-2 in human gastric mucosa.
The CagA protein of Helicobacter pylori is translocated into epithelial cells and binds to SHP-2 in human gastric mucosa.
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DOI：
10.1086/367807
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发表时间：
2003-01
期刊：
影响因子：
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通讯作者：
S. Yamazaki;A. Yamakawa;Yoshiyuki Ito;M. Ohtani;H. Higashi;M. Hatakeyama;T. Azuma
中科院分区：
文献类型：
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作者：
S. Yamazaki;A. Yamakawa;Yoshiyuki Ito;M. Ohtani;H. Higashi;M. Hatakeyama;T. Azuma
最近的实验表明，幽门螺杆菌的CagA通过IV型分泌系统注入上皮细胞并在细胞中经历酪氨酸磷酸化，并且易位的CagA结合含有SRC同源2结构域的酪氨酸磷酸酶（SHP-2）。我们研究了这些现象在体内人体胃粘膜。在H. pylori阳性的萎缩性胃炎患者和H.幽门阳性的早期胃癌患者。相反，CagA在肠上皮化生或癌的胃粘膜中未检测到。我们的研究结果提供了第一个证据，CagA易位到胃上皮细胞，接受酪氨酸磷酸化，并结合SHP-2在体内人胃粘膜。SHP-2的失调CagA可能发挥作用，在收购的细胞转化表型在一个相对较早的阶段，多步骤胃癌。
Recent experiments have indicated that CagA of Helicobacter pylori is injected into epithelial cells via the type IV secretion system and undergoes tyrosine phosphorylation in cells and that translocated CagA binds the SRC homology 2 domain-containing tyrosine phosphatase (SHP-2). We investigated these phenomena in in vivo human gastric mucosa. Tyrosine-phosphorylated CagA and CagA-coimmunoprecipitated SHP-2 were detected in gastric mucosa from H. pylori-positive patients with atrophic gastritis and in noncancerous tissues from H. pylori-positive patients with early gastric cancer. In contrast, CagA was not detected in gastric mucosa with either intestinal metaplasia or cancer. Our results provide the first evidence that CagA is translocated into the gastric epithelial cells, receives tyrosine phosphorylation, and binds SHP-2 in in vivo human gastric mucosa. Deregulation of SHP-2 by CagA may play a role in the acquisition of a cellular-transformed phenotype at a relatively early stage of multistep gastric carcinogenesis.