Figure 2

Schematic overview of the integrin signaling. (A) Signaling pathways downstream of FAK and Src controlling actin cytoskeletal rearrangement and FAs. Integrin activation induces recruitment and stimulation of FAK and Src, which target RhoA or Rac1 and Cdc42 GTPases, thereby controlling cell migration and elongation via regulation of the actin cytoskeleton. The elongated cell morphology might also be caused by deregulated FAs. (B) Detailed mechanism of CagL-induced integrin signaling leading to cell elongation and reorganization of the actin cytoskeleton. FAK and Src are activated via integrin-CagL (L) interaction leading to the injection of the pathogenic factor CagA. CagA is initially phosphorylated by Src, which then interacts with Shp-2 and Csk to inactivate FAK and Src at later time points. Inactivation of Src leads to the dephosphorylation of ezrin, vinculin and cortactin, while CagA tyrosine phosphorylation is maintained by activated Abl kinases. These processes contribute to the deregulation of FA disassembly leading to host cell elongation. In parallel, FAK and Src control the actin cytoskeleton via the CrkII/DOCK180/Rac1/WAVE/Arp2/3 pathway, which affects cell migration. This pathway is controlled by Abl kinases, paxillin or p130Cas. Red arrowheads:H. pylori-associated signaling pathways; black arrowheads: FAK- and Src-associated signaling pathways.