Role of Abl and Src family kinases in actin-cytoskeletal rearrangements induced by the Helicobacter pylori CagA protein.
The clinical outcome of infections with Helicobacter pylori is determined by a complex interplay of host-pathogen interactions, and persistent infection with this pathogen is the major cause of developing chronic gastritis, peptic ulcers and gastric cancer. Highly virulent strains encode a so-called type IV secretion system which translocates the CagA effector protein into gastric epithelial target cells. Injected CagA becomes tyrosine-phosphorylated on EPIYA sequence motifs by Src and Abl family kinase members. CagA then binds to and activates/inactivates various signalling proteins in a phosphorylation-dependent and phosphorylation-independent manner. In this way injected CagA can act as a master key that evolved during evolution the ability to highjack multiple downstream signalling cascades. Here we review our knowledge on the tyrosine phosphorylation motifs in CagA, the recent advances in the interaction of CagA with Src and Abl tyrosine kinases and their role in signalling events leading to changes of the phosphorylation status of actin-binding proteins cortactin, ezrin and vinculin followed by actin-cytoskeletal rearrangements, cell scattering and elongation. Detailed investigation of these pathways will help to yield novel insights and to elucidate the mechanisms of H. pylori-induced pathogenesis.
University of Magdeburg, Department of Medical Microbiology, Leipziger Str. 44, D-39120 Magdeburg, Germany.
Nicole
N
Tegtmeyer
Steffen
S
Backert
D000199:Actins / Q000378:metabolism*; D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D016481:Helicobacter Infections / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
D000199:Actins; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori; D016315:Proto-Oncogene Proteins c-abl; D019061:src-Family Kinases