The Helicobacter pylori CagA protein induces tyrosine dephosphorylation of ezrin.
Helicobacter pylori is one of the most wide-spread bacterial pathogens and infects the human stomach to cause diseases, such as gastritis, gastric ulceration, and gastric cancer. A major virulence determinant is the H. pylori CagA protein (encoded by the cytotoxin-associated gene A) which is translocated from the bacteria into the cytoplasm of host cells by a type IV secretion system. In the host cell, CagA is phosphorylated on tyrosine residues and induces rearrangements of the actin cytoskeleton. We have previously shown that tyrosine-phosphorylated CagA inhibits the catalytic activity of Src family kinases and induces tyrosine dephosphorylation of several host cell proteins. Here, we identified one of these proteins as ezrin by a combination of preparative gel electrophoresis, two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS). Specific pharmacological inhibition of Src family kinases also induces ezrin dephosphorylation. Therefore, ezrin dephosphorylation appears to be induced by CagA-mediated Src inactivation. Ezrin is the founding member of the ezrin-radixin-moesin (ERM) family of proteins which are signalling integrators at the cell cortex. Since ezrin is a component of microvilli and a linker protein between actin filaments and membrane proteins, this observation has important implications for H. pylori pathogenesis and might also help to explain the development of gastric cancer.
Selbach
Matthias
M
Max-Planck-Institut für Infektionsbiologie, Abt. Molekulare Biologie, Berlin, Germany.
Moese
Stefan
S
Backert
Steffen
S
Jungblut
Peter R
PR
Meyer
Thomas F
TF
D000199:Actins / Q000378:metabolism; D000942:Antigens, Bacterial / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D003598:Cytoskeletal Proteins; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D010750:Phosphoproteins / Q000737:chemistry*; D010766:Phosphorylation; D020543:Proteome; D034622:RNA Interference; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013274:Stomach Neoplasms / Q000382:microbiology; D014238:Trichloroacetic Acid / Q000494:pharmacology; D014443:Tyrosine / Q000737:chemistry*; D019061:src-Family Kinases / Q000378:metabolism; D000099149:Ezrin
D000199:Actins; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; D010750:Phosphoproteins; D020543:Proteome; D014238:Trichloroacetic Acid; D014443:Tyrosine; D019061:src-Family Kinases; D000099149:Ezrin; C080866:cagA protein, Helicobacter pylori