Cytotoxin-associated gene A protein (CagA) (CagA)

Cytotoxin-associated gene A (CagA) is a major virulence factor and the first identified bacterial oncoprotein, produced by highly pathogenic strains of Helicobacter pylori. Following bacterial attachment to gastric epithelial cells, CagA is translocated into the host cytoplasm via a type IV secretion system (T4SS). Once intracellular, it undergoes tyrosine phosphorylation by host Src and Abl family kinases at specific EPIYA motifs, allowing it to act as a non-physiological scaffold that hijacks various signaling pathways. Primarily, it interacts with the protein tyrosine phosphatase SHP2, leading to sustained MAPK/ERK activation, which drives abnormal cell proliferation, motility, and the characteristic 'hummingbird' morphological phenotype. CagA also interacts with polarity-regulating kinases and tumor suppressors like ASPP2 to promote epithelial-to-mesenchymal transition and genomic instability. Its presence is strongly correlated with an increased risk of gastric adenocarcinoma, peptic ulcers, and MALT lymphoma. Due to its central role in H. pylori-induced malignancy and the rising challenge of antibiotic resistance, CagA is a high-priority therapeutic target for the development of virulence-attenuating drugs and prophylactic vaccines.

Other names

Cytotoxin-associated antigen ACagA antigenCagA oncoproteinP128128 kDa immunodominant antigenBacterial oncoprotein CagA

Inhibition of CagA delivery by targeting the bacterial type IV secretion system (T4SS), prevention of intracellular tyrosine phosphorylation by host-cell kinases, disruption of pathogenic protein-protein interactions with host effectors such as SHP2 or ASPP2, and vaccine-induced neutralizing antibody production.