Orchestration of aberrant epithelial signaling by Helicobacter pylori CagA.
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.
Peek
Richard M
RM
Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2279, USA. richard.peek@vanderbilt.edu <richard.peek@vanderbilt.edu>
D000230:Adenocarcinoma / Q000209:etiology / Q000382:microbiology; D000818:Animals; D000942:Antigens, Bacterial / Q000502:physiology*; D001426:Bacterial Proteins / Q000502:physiology*; D000081247:CSK Tyrosine-Protein Kinase; D004847:Epithelial Cells / Q000382:microbiology* / Q000502:physiology; D005753:Gastric Mucosa / Q000382:microbiology; D005756:Gastritis / Q000382:microbiology / Q000503:physiopathology; D016481:Helicobacter Infections / Q000382:microbiology / Q000503:physiopathology; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D051379:Mice; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013274:Stomach Neoplasms / Q000209:etiology / Q000382:microbiology; D019061:src-Family Kinases
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D047908:Intracellular Signaling Peptides and Proteins; C080866:cagA protein, Helicobacter pylori; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse