CagA (Cytotoxin-Associated Gene A)

  • CagA is a protein that is encoded by the cagA gene in certain Helicobacter pylori. Such Helicobacter pylori are described as cagA-positive Helicobacter pylori (Type I). 
  • CagA was initially suggested to be responsible for the vacuole-inducing phenotype in HeLa cells by Helicobacter pylori, hence named cytotoxin-associated gene A (Cover et al., 1990). However, later it was found not to be responsible for this phenotype as the phenotype persisted even after knocking out the CagA gene (Tummuru et al., 1994).
  • The CagA gene was cloned in 1993. (Tummuru et al., 1993)
  • CagA-positive Helicobacter pylori are associated with severe clinical outcomes. 
  • CagA is transported to host cells (gastric epithelial cells) by Type 4 secretory system (T4SS) by CagA-positive Helicobacter pylori strains. 
  • Once inside the host cells, CagA is localized to the host cell membrane. It may also undergo tyrosine phosphorylation by host kinases (Src and Abl family of tyrosine kinases).
  • Both phosphorylated and unphosphorylated CagA are shown to interact with several host proteins which can lead to severe dysregulation of signaling pathways and physiology of host cells.
  • One of the host proteins SH2 domain-containing phosphatase SHP-2 has been shown to be necessary for the induction of Hummingbird phenotype in gastric epithelial cell line AGS.

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

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