Figure 1. Model for the translocation of CagA into host cells and role in subverting multiple host signaling cascades.

(A) CagA phosphorylation-independent and (B) phosphorylation-dependent signal transduction events are displayed. Black arrows depict activated signaling events and red lines correspond to inhibitory pathways. Using a type IV secretion system (Cag-pilus), H. pylori delivers CagA across both bacterial and host cell membranes into gastric epithelial cells. Translocation requires integrin α₅β₁ and phosphatidylserine. Upon delivery, members of the oncogenic c-Src and c-Abl tyrosine kinases can phosphorylate CagA at EPIYA and EPIYT sequences. Intracellular CagA then modulates multiple signaling cascades associated with cell polarity, cell cycle, cell proliferation, disruption of tight and adherent junctions, cytoskeletal rearrangements, cell elongation, pro-inflammatory responses and suppression of apoptosis, as indicated. The phospho-EPIYT-motif differs from phospho-EPIYA as it leads to enhanced Akt kinase activation (*) and suppression of IL-8 secretion and AGS cell elongation (9). Panels A and B were updated from Backert and co-workers (2010, Helicobacter 15: 163–176) with kind permission from Wiley.