Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10815725 | Cellular Signalling | 2010 | 9 Pages |
Abstract
It is supposed that human pathogens, e.g. Helicobacter pylori abuse lipid raft domains on the host cell plasma membrane to infect the cell. Investigating DRM-associated molecules we identified the transmembrane adapter proteins (TRAPs), non-T cell activation linker (NTAL) and lymphocyte-specific protein tyrosine kinase (Lck)-interacting membrane protein (LIME) to be regulated by H. pylori in the human epithelial cell line HCA-7. Up to now, raft-associated TRAPs were exclusively described to mediate signal propagation downstream of antigen receptors. Our results posed the question whether these proteins adopt a role in H. pylori-infected epithelial cells too. Our studies revealed that H. pylori induces tyrosine phosphorylation of NTAL as well as LIME within 15Â min of infection. We observed that activated NTAL and LIME bind to the Src homology 2 (SH2)-domain of growth factor receptor-bound protein 2 (Grb2) within 15 to 30Â min of infection and associate with the c-Met receptor. Further, NTAL has a contributory role in regulating H. pylori-induced extracellular signal-regulated kinase (ERK) activation. After suppression of NTAL protein levels by siRNA, ERK phosphorylation was reduced to approximately 50%. Additionally, the knockdown of NTAL suppressed the phosphorylation of cytosolic phospholipase A2 (cPLA2). Activated cPLA2 catalyzes the release of arachidonic acid (AA), whose metabolites are pivotal mediators in the H. pylori-induced inflammatory response. Thus, we propose that NTAL participates in the activation of the c-Met-Grb2-ERK-cPLA2 signalling cascade at early stages of H. pylori infection.
Keywords
EGFRNTALCSKGRB2T4SSSH2VacAHGFDRMSFKcPLA2PAGTRAPPGE2PBMCERKCOX-2c-MetSmall interfering RNAsiRNALimeArachidonic acidPAIvacuolating toxincag pathogenicity islandLATType IV secretion systemCyclooxygenase-2Hepatocyte growth factorPhosphorylationcytosolic phospholipase A2Linker for activation of T cellsSrc Homology 2growth factor receptor-bound protein 2Prostaglandin E2Src-family kinaseextracellular signal-regulated kinaseEpidermal growth factor receptor
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Cornelia Rieke, Thilo Kähne, Katrin Schweitzer, Burkhart Schraven, Jürgen Wienands, Michael Engelke, Michael Naumann,