© 2005 Japanese Cancer Association Blackwell Publishing AsiaReview Article Helicobacter pylori CagA: a new paradigm for bacterial carcinogenesis

Infection with cagA-positive Helicobacter pylori is associated with the development of gastric adenocarcinoma. The cagA gene product CagA is injected directly from the bacterium into the bacterium-attached gastric epithelial cells via the type-IV secretion system. Upon membrane localization and subsequent tyrosine phosphorylation by Src family kinases, CagA functions as a scaffolding adaptor and interacts with a number of host proteins that regulate cell growth, cell motility and cell polarity in both CagA phosphorylation-dependent and phosphorylation-independent manners. Of special interest is the interaction of CagA with the SHP-2 tyrosine phosphatase, gain-of-function mutations that of which have recently been found in a variety of human malignancies. The CagA–SHP-2 interaction is entirely dependent on CagA tyrosine phosphorylation and, through the complex formation, SHP-2 is catalytically activated and induce