Item Type: | Article |
---|---|
Title: | The Helicobacter pylori CagA protein induces tyrosine dephosphorylation of ezrin |
Creators Name: | Selbach, M., Moese, S., Backert, S., Jungblut, P.R. and Meyer, T.F. |
Abstract: | 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. |
Keywords: | Actin cytoskeleton, Ezrin-radixin-moesin family, Molecular pathogenesis, Src, Type IV secretion |
Source: | Proteomics |
ISSN: | 1615-9853 |
Publisher: | Wiley |
Volume: | 4 |
Number: | 10 |
Page Range: | 2961-2968 |
Date: | October 2004 |
Official Publication: | https://doi.org/10.1002/pmic.200400915 |
PubMed: | View item in PubMed |
Repository Staff Only: item control page