RT Journal Article SR Electronic T1 Orchestration of Aberrant Epithelial Signaling by Helicobacter pylori CagA JF Science's STKE JO Sci. STKE FD American Association for the Advancement of Science SP pe14 OP pe14 DO 10.1126/stke.2772005pe14 VO 2005 IS 277 A1 Peek, Richard M. YR 2005 UL http://stke.sciencemag.org/content/2005/277/pe14.abstract AB Persistent colonization by Helicobacter pylori is the strongest risk factor for distal gastric adenocarcinoma, and H. pylori strains that harbor the cag pathogenicity island further augment cancer risk. The H. pylori cag island encodes a secretion system, and the product of the terminal gene in the island (CagA) is translocated into host epithelial cells after bacterial attachment, where it undergoes tyrosine phosphorylation by Src kinases and binds the eukaryotic phosphatase SHP-2. Higashi et al. now demonstrate that CagA-dependent SHP-2 activation leads to sustained activation of ERK (extracellular signal-regulated kinase), culminating in morphological changes that mimic unrestrained stimulation by growth factors. These data implicate the cag island as a key mediator of pathogenic epithelial responses that may heighten the risk for gastric cancer.