Helicobacter pylori ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, microaerophilic, spiral (helical) bacterium usually found in the stomach. Its helical shape (from which the genus name, helicobacter, derives) is thoug ...

'' virulence factor CagA (cytotoxin-associated gene A) is a 120–145kDa protein encoded on the 40kb ''cag''

pathogenicity island Pathogenicity islands (PAIs), as termed in 1990, are a distinct class of genomic islands acquired by microorganisms through horizontal gene transfer. Pathogenicity islands are found in both animal and plant pathogens. Additionally, PAIs are found ...

(PAI). ''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. 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 kinase Src kinase family is a family of non-receptor tyrosine kinases that includes nine members: Src, Yes, Fyn, and Fgr, forming the SrcA subfamily, Lck, Hck, Blk, and Lyn in the SrcB subfamily, and Frk in its own subfamily. Frk has homologs ...

s (e.g.

Fyn Funen ( da, Fyn, ), with an area of , is the third-largest island of Denmark, after Zealand and Vendsyssel-Thy. It is the 165th-largest island in the world. It is located in the central part of the country and has a population of 469,947 as ...

and Lyn).

Role in Cancer

''H. pylori'' infection is associated with

MALT lymphoma MALT lymphoma (MALToma) is a form of lymphoma involving the mucosa-associated lymphoid tissue (MALT), frequently of the stomach, but virtually any mucosal site can be affected. It is a cancer originating from B cells in the marginal zone of the MAL ...

and

gastric adenocarcinoma Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lym ...

and CagA is thought to be involved in cancer development. 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". This phenotype mimics an effect produced by

hepatocyte growth factor Hepatocyte growth factor (HGF) or scatter factor (SF) is a paracrine cellular growth, motility and morphogenic factor. It is secreted by mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells, but also acts on ...

which may participate in various aspects of cancer, including

metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then ...

. CagA is also a highly antigenic protein that is associated with a prominent inflammatory response by eliciting interleukin-8 production.

The ''Cag'' PAI

References

External links

* {{cite web , title=Search: "cytotoxin-associated gene A" "Helicobacter pylori" , work=Protein , publisher=NCBI , url=https://www.ncbi.nlm.nih.gov/protein/?term=%22cytotoxin-associated+gene+A%22+%22Helicobacter+pylori%22 Virulence factors Helicobacter pylori Infectious causes of cancer