Helicobacter pylori CagA protein targets the c-Met receptor and enhances the motogenic response

作者：Yuri Churin, Laila Al-Ghoul, Oliver Kepp, Thomas F. Meyer, Walter Birchmeier, Michael Naumann · 发表于：The Journal of Cell Biology · 年份：2003 · DOI：10.1083/jcb.200208039 · 被引用次数：355 · 研究领域：Helicobacter pylori-related gastroenterology studies、Veterinary medicine and infectious diseases、Liver physiology and pathology

Infection with the human microbial pathogen Helicobacter pylori is assumed to lead to invasive gastric cancer. We find that H. pylori activates the hepatocyte growth factor/scatter factor receptor c-Met, which is involved in invasive growth of tumor cells. The H. pylori effector protein CagA intracellularly targets the c-Met receptor and promotes cellular processes leading to a forceful motogenic response. CagA could represent a bacterial adaptor protein that associates with phospholipase Cgamma but not Grb2-associated binder 1 or growth factor receptor-bound protein 2. The H. pylori-induced motogenic response is suppressed and blocked by the inhibition of PLCgamma and of MAPK, respectively. Thus, upon translocation, CagA modulates cellular functions by deregulating c-Met receptor signaling. The activation of the motogenic response in H. pylori-infected epithelial cells suggests that CagA could be involved in tumor progression.