Schematic overview of CagL and CagA-mediated signal transduction pathways involved in H. pylori -induced cell motility and elongation. (A) H. pylori expresses CagL at the tip of the T4SS that directly binds to β1 integrins presented on gastric epithelial cells. Activated β1 integrin stimulates FAK and Src activity in early phases of H. pylori infections. FAK phosphorylates paxillin upon infection which might contribute to c-Abl-phosphorylated Crk signaling, which could be influenced by SFK activity via paxillin or p130CAS. FAK, SFKs and Abl kinase-mediated activation of Crk proteins can regulate the actin cytoskeleton through the DOCK180/Rac1/WAVE/Arp2/3 pathway contributing to epithelial cell migration. (B) CagL-integrin binding leads to the translocation of the H. pylori pathogenic factor CagA into the host cytoplasm. CagA is rapidly phosphorylated by kinases of the Src family (SFK) and bind to a large number of host cells factors (X) in its phosphorylated and non-phosphorylated form. Tyrosine phosphorylated CagA interacts with Shp-2 and Csk to inactivate FAK and Src in late phases of H. pylori infection. While inactivated Src is replaced by activated Abl kinases to maintain CagA phosphorylation, inactive Src leads to tyrosine dephosphorylation of Src target molecules ezrin, vinculin and cortactin. Cortactin is then serine phosphorylated by H. pylori-activated ERK1/2 kinases, which crucially contributes to cell elongation. Black arrows, H. pylori-induced direct signaling pathways. Dotted arrows, H. pylori-induced or Src-mediated indirect signaling pathways. Grey arrows, inactivating signaling pathways. Red arrow, CagA injection as the central step in the regulation of focal adhesions. P, phosphorylated proteins. X, host cell proteins.