Cytotoxin-associated gene A (CagA) (CagA)

Cytotoxin-associated gene A (CagA) is a critical virulence factor and the first identified bacterial oncoprotein, primarily produced by Helicobacter pylori. It is delivered into host gastric epithelial cells through a specialized type IV secretion system (T4SS), which functions like a molecular syringe. Once inside the cytoplasm, CagA undergoes tyrosine phosphorylation by host Src and Abl family kinases at specific EPIYA motifs. It then acts as a non-physiological scaffold protein, interacting with and deregulating multiple host signaling molecules, most notably the SHP-2 tyrosine phosphatase and the PAR1/MARK2 kinase. These interactions lead to significant alterations in host cell physiology, including the disruption of apical-basal polarity, loss of cell-to-cell adhesion, and the induction of a characteristic elongated hummingbird phenotype. These changes promote chronic inflammation, epithelial-to-mesenchymal transition (EMT), and uncontrolled cell proliferation, which are key drivers of gastric carcinogenesis. Consequently, infection with CagA-positive H. pylori strains is the strongest known risk factor for the development of gastric adenocarcinoma and peptic ulcer disease. While no drugs currently target CagA directly in clinical practice, it is a major focus for the development of novel inhibitors and vaccines aimed at preventing H. pylori-associated cancers.

Other names

Cytotoxin-associated antigenCagA proteinP128Bacterial oncoprotein CagACytotoxin-associated gene A protein

CagA is translocated into host gastric epithelial cells via a type IV secretion system (T4SS), where it is phosphorylated by host Src and Abl kinases at EPIYA motifs. It then acts as a scaffold protein, activating SHP-2 phosphatase and disrupting PAR1/MARK2 signaling, which leads to deregulation of cell polarity, adhesion, and proliferation.