Cytotoxicity-associated immunodominant antigen (CagA), also CAG pathogenicity island protein 26, is a 120–145kDa protein encoded on the 40kb CAG pathogenicity island of Helicobacter pylori.^[1] CagA is the major virulence factor of H. pylori.

H. pylori strains can be divided into CagA positive or negative strains. Approximately 60% of H. pylori strains isolated in Western countries carry cag PAI, whereas almost all of the East Asian isolates are cag PAI-positive.^{[1][dubious – discuss]}

The cag PAI also encodes for a type IV secretion system which is used to "inject" CagA into a target cell upon H. pylori attachment. After translocation, CagA localises to the inner surface of the cell membrane and undergoes tyrosine phosphorylation by Src family kinases (e.g. Fyn and Lyn).^[1]

Role in cancer

H. pylori infection is associated with MALT lymphoma and gastric adenocarcinoma and CagA is thought to be involved in cancer development.^[2] Phosphorylated CagA is able to interact with the SHP-2 tyrosine phosphatase, rendering it functionally active, triggering a host cell morphological change to a more motile phenotype known as the "hummingbird phenotype".^[1] This phenotype mimics an effect produced by hepatocyte growth factor which may participate in various aspects of cancer, including metastasis.^[2] CagA is also a highly antigenic protein that is associated with a prominent inflammatory response by eliciting interleukin-8 production.^[3]

The Cag PAI