RRC ID 17600
Author Tabassam FH, Graham DY, Yamaoka Y.
Title Paxillin is a novel cellular target for converging Helicobacter pylori-induced cellular signaling.
Journal Am. J. Physiol. Gastrointest. Liver Physiol.
Abstract Paxillin is involved in the regulation of Helicobacter pylori-mediated gastric epithelial cell motility. We investigated the signaling pathways regulating H. pylori-induced paxillin phosphorylation and the effect of the H. pylori virulence factors cag pathogenicity island (PAI) and outer inflammatory protein (OipA) on actin stress fiber formation, cell phenotype, and IL-8 production. Gastric cell infection with live H. pylori induced site-specific phosphorylation of paxillin tyrosine (Y) 31 and Y118 in a time- and concentration-dependent manner. Activated paxillin localized in the cytoplasm at the tips of H. pylori-induced actin stress fibers. Isogenic oipA mutants significantly reduced paxillin phosphorylation at Y31 and Y118 and reduced actin stress fiber formation. In contrast, cag PAI mutants only inhibited paxillin Y118 phosphorylation. Silencing of epidermal growth factor receptor (EGFR), focal adhesion kinase (FAK), or protein kinase B (Akt) expression by small-interfering RNAs or inhibiting kinase activity of EGFR, Src, or phosphatidylinositol 3-kinase (PI3K) markedly reduced H. pylori-induced paxillin phosphorylation and morphologic alterations. Reduced FAK expression or lack of Src kinase activity suppressed H. pylori-induced IL-8 production. Compared with infection with the wild type, infection with the cag PAI mutant and oipA mutant reduced IL-8 production by nearly 80 and 50%. OipA-induced IL-8 production was FAK- and Src-dependent, although a FAK/Src-independent pathway for IL-8 production also exists, and the cag PAI may be mainly involved in this pathway. We propose paxillin as a novel cellular target for converging H. pylori-induced EGFR, FAK/Src, and PI3K/Akt signaling to regulate cytoskeletal reorganization and IL-8 production in part, thus contributing to the H. pylori-induced diseases.
Volume 301(4)
Pages G601-11
Published 2011-10
DOI 10.1152/ajpgi.00375.2010
PII ajpgi.00375.2010
PMID 21757638
PMC PMC3191551
MeSH Actins / metabolism* Antigens, Bacterial / physiology Bacterial Outer Membrane Proteins / physiology* Bacterial Proteins / physiology Cell Line Epithelial Cells / microbiology Focal Adhesion Kinase 1 / physiology* Genomic Islands Helicobacter Infections / metabolism Helicobacter Infections / physiopathology* Helicobacter pylori / genetics Helicobacter pylori / metabolism* Humans Interleukin-8 / biosynthesis* Paxillin / physiology* Phosphatidylinositol 3-Kinases / physiology* Phosphorylation Receptor, Epidermal Growth Factor / physiology* Signal Transduction / physiology
IF 3.293
Times Cited 12
Human and Animal Cells MKN45 (RCB1001)