Cytotoxin-associated gene A protein (CagA)

Cytotoxin-associated gene A (CagA) is a 120-145 kDa protein and a major virulence factor of Helicobacter pylori, often termed a 'bacterial oncoprotein' due to its strong association with gastric adenocarcinoma (PubMed: 25151268). The protein is delivered into host gastric epithelial cells through a specialized Type IV secretion system, where it undergoes tyrosine phosphorylation by host kinases such as Src and Abl at specific EPIYA motifs (UniProt: P12914). Once phosphorylated, CagA binds to the host protein tyrosine phosphatase SHP-2, inducing sustained signaling that promotes abnormal cell proliferation, motility, and survival (NCBI: NBK2433). Beyond its interaction with SHP-2, CagA disrupts cell-to-cell junctions and apical-basal polarity by binding to proteins like E-cadherin and PAR1b, facilitating the transformation of the gastric mucosa (PubMed: 12154420). While no drugs currently target CagA directly in clinical practice, the standard treatment involves the eradication of CagA-producing H. pylori using antibiotic combinations like clarithromycin and amoxicillin. Research is currently exploring small molecule inhibitors that could block the CagA-SHP2 interaction or prevent the delivery of the protein into host cells to mitigate cancer risk in infected individuals (PubMed: 32661338).

Other names

Protein CagACagA effector proteinp120Bacterial oncoprotein CagA

CagA acts as a bacterial oncoprotein that is injected into host gastric epithelial cells via a Type IV secretion system. Inside the host, it is phosphorylated by Src and Abl kinases at EPIYA motifs, allowing it to bind and constitutively activate the SHP-2 tyrosine phosphatase (PubMed: 12154420). It also interacts with PAR1b/MARK2 to disrupt apical-basal polarity and with E-cadherin to promote epithelial-mesenchymal transition-like changes (UniProt: P12914).