title: Multistep activation of the Helicobacter pylori effector CagA.
abstract: Chronic infection with the Gram-negative bacterium Helicobacter pylori is a major risk factor for the development of gastric cancer. Accumulating evidence indicates that the H. pylori virulence determinant cytotoxin-associated gene A (CagA) has a key oncogenic role in the process. Certain biological activities of CagA require its tyrosine phosphorylation by host cell kinases. In this issue of the JCI, Mueller and colleagues report their detailed kinetic and functional analysis of CagA phosphorylation, which indicates that c-Src and c-Abl kinases sequentially phosphorylate CagA. Interestingly, the two phosphorylation events need not occur on the same CagA molecule but are both required for the biological effects of CagA. The results provide a clinically relevant example of how a successful bacterial pathogen has evolved to exploit the tightly coordinated, sequential activity of host cell kinases for virulence factor activation and induction of pathology.
authors.affiliation: Institute of Molecular Cancer Research, University of Zürich, Zürich, Switzerland. mueller@imcr.uzh.ch
authors.forename: Anne
authors.initials: A
authors.lastname: Müller
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D000081247:CSK Tyrosine-Protein Kinase; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D019061:src-Family Kinases
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D016315:Proto-Oncogene Proteins c-abl; D019061:src-Family Kinases; C000631346:CSK protein, human