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J. Biol. Chem., Vol. 277, Issue 9, 6775-6778, March 1, 2002
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,
From the Max-Planck-Institut für Infektionsbiologie, Abt.
Molekulare Biologie, Schumannstrasse 20/21, D-10117 Berlin and the
The gastric pathogen Helicobacter
pylori uses a type IV secretion system to inject the bacterial
CagA protein into gastric epithelial cells. Within the host cell, CagA
becomes phosphorylated on tyrosine residues and initiates cytoskeletal
rearrangements. We demonstrate here that Src-like protein-tyrosine
kinases mediate CagA phosphorylation in vitro and in
vivo. First, the Src-specific tyrosine kinase inhibitor PP2
specifically blocks CagA phosphorylation and cytoskeletal
rearrangements thereby inhibiting the CagA-induced hummingbird
phenotype of gastric epithelial cells. Second, CagA is in
vivo phosphorylated by transiently expressed c-Src. Third, recombinant c-Src and lysates derived from c-Src-expressing fibroblasts but not lysates derived from Src-, Yes-, and Fyn-deficient cells phosphorylated CagA in vitro. Fourth, a transfected
CagA-GFP fusion protein is phosphorylated in vivo in
Src-positive fibroblasts but not in Src-, Yes-, and Fyn-deficient
cells. Because a CagA-GFP fusion protein mutated in an EPIYA
motif is not efficiently phosphorylated in any of these fibroblast
cells, the CagA EPIYA motif appears to constitute the major c-Src
phosphorylation site conserved among CagA-positive
Helicobacter strains.
Zentrum für Infektionsforschung, Universität
Würzburg, Röntgenring 11, D-97070 Würzburg,
Germany
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