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c‐Src/Lyn kinases activate Helicobacter pylori CagA through tyrosine phosphorylation of the EPIYA motifs
Author(s) -
Stein Markus,
Bagnoli Fabio,
Halenbeck Robert,
Rappuoli Rino,
Fantl Wendy J.,
Covacci Antonello
Publication year - 2002
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.2002.02781.x
Subject(s) - lyn , caga , biology , proto oncogene tyrosine protein kinase src , helicobacter pylori , phosphorylation , tyrosine kinase , protein tyrosine kinases , tyrosine protein kinase csk , kinase , cancer research , tyrosine phosphorylation , sh2 domain , tyrosine , microbiology and biotechnology , genetics , biochemistry , signal transduction , gene , virulence
Summary The human pathogen Helicobacter pylori colonizes the mucous layer of the stomach. During parasitic infection, freely swimming bacteria adhere to the gastric epithelial cells and trigger intracellular signalling pathways. This process requires the translocation of the effector protein CagA into the host cell through a specialized type IV secretion system encoded in the cag pathogenicity island. Following transfer, CagA is phosphorylated on tyrosine re‐sidues by a host cell kinase. Here, we describe how the tyrosine phosphorylation of CagA is restricted to a previously identified repeated sequence called D1. This sequence is located in the C‐terminal half of the protein and contains the five‐amino‐acid motif EPIYA, which is amplified by duplications in a large fraction of clinical isolates. Tyrosine phosphorylation of CagA is essential for the activation process that leads to dramatic changes in the morphology of cells growing in culture. In addition, we observed that two members of the src kinases family, c‐Src and Lyn, account for most of the CagA‐specific kinase activity in host cell lysates. Thus, CagA translocation followed by tyrosine phosphorylation at the EPIYA motifs promotes a growth factor‐like response with intense cytoskeletal rearrangements, cell elongation effects and increased cellular motility.