• CagA (Cytotoxin-Associated Gene A) is a protein encoded by the cagA gene found in specific strains of Helicobacter pylori, which are referred to as cagA-positive Helicobacter pylori (Type I Helicobacter pylori strains). 
• CagA-positive Helicobacter pylori strains are associated with severe clinical outcomes. 
• CagA was originally proposed to be responsible for the vacuole-inducing phenotype in HeLa cells caused by Helicobacter pylori, hence named cytotoxin-associated gene A (Cover et al., 1990). However, subsequent studies revealed that CagA is not responsible for this phenotype, as the vacuole-inducing effect persisted even after the CagA gene was knocked out (Tummuru et al., 1994).
  
• The CagA gene was successfully cloned in 1993 (Tummuru et al., 1993).  It is located on a specific genomic region known as the cag Pathogenicity Island (CagPAI) (Censini et al., 1996, Akopyants et al., 1998). The gene size ranges from 3,200 to 3,800 nucleotides (140 kDa), while the protein has a molecular weight of approximately 120 kDa to 140 kDa.
• CagA is transported into host gastric epithelial cells by the Type 4 secretory system (T4SS) of CagA-positive Helicobacter pylori strains.
• Once inside the host cells, CagA is localized to the host cell membrane and can undergo tyrosine phosphorylation by host kinases, including the Src and Abl family of tyrosine kinases.
• Both phosphorylated and unphosphorylated CagA are known to interact with several host proteins, which can lead to severe dysregulation of signaling pathways and the physiology of host cells.
• CagA can deregulate several host signaling pathways including MAPK/ERK, PI3K/AKT, and Wnt/β-catenin signalling pathways.
  
• One of the host proteins, SH2 domain-containing phosphatase SHP-2, has been shown to be necessary for the induction of the Hummingbird phenotype in the gastric epithelial cell line AGS.
• CagA is the first identified bacterial-derived oncoprotein.
  

REFERENCES

• Cover et al., 1990. Characterization of and human serologic response to proteins in Helicobacter pylori broth culture supernatants with vacuolizing cytotoxin activity. Infect Immun. 58(3), 603-610. PMID-2307514; Full-Text Links: asm, PMC258508   
• Tummuru et al., 1993. Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. Infect Immun. 61(5), 1799-809. PMID-8478069; Full-Text Links: asm, PMC280768
• Tummuru et al., 1994. Mutation of the cytotoxin-associated cagA gene does not affect the vacuolating cytotoxin activity of Helicobacter pylori. Infect Immun. 62(6), 2609-13. PMID-8188385; Full-Text Links: asm, PMC186552