CagA
Helicobacter pylori virulence factor CagA (cytotoxin-associated gene A) is a 120–145kDa protein encoded on the 40kb cag pathogenicity island (PAI).[1] H. pylori strains can be divided into CagA positive or negative strains. Around 60% of H. pylori isolates in Western countries are positive, whereas the majority of East Asian isolates are positive.[1]
The cag PAI also encodes for a type 4 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]
References
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