Open AccessHelicobacter pylori and mitogen‐activated protein kinases mediate activator protein‐1 (AP‐1) subcomponent protein expression and DNA‐binding activity in gastric epithelial cells
Author(s) -
Ding SongZe,
Olekhnovich Igor N.,
Cover Timothy L.,
Peek Richard M.,
Smith Michael F.,
Goldberg Joanna B.
Publication year - 2008
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1111/j.1574-695x.2008.00439.x
Subject(s) - biology , mapk/erk pathway , protein kinase a , kinase , junb , caga , microbiology and biotechnology , p38 mitogen activated protein kinases , helicobacter pylori , activator (genetics) , fosb , gene expression , gene , biochemistry , genetics , virulence
Emerging evidence has suggested a critical role for activator protein‐1 (AP)‐1 in regulating various cellular functions. The goal of this study was to investigate the effects of Helicobacter pylori and mitogen‐activated protein kinases (MAPK) on AP‐1 subcomponents expression and AP‐1 DNA‐binding activity in gastric epithelial cells. We found that H. pylori infection resulted in a time‐ and dose‐dependent increase in the expression of the proteins c‐Jun, JunB, JunD, Fra‐1, and c‐Fos, which make up the major AP‐1 DNA‐binding proteins in AGS and MKN45 cells, while the expression levels of Fra‐2 and FosB remained unchanged. Helicobacter pylori infection and MAPK inhibition altered AP‐1 subcomponent protein expression and AP‐1 DNA‐binding activity, but did not change the overall subcomponent composition. Different clinical isolates of H. pylori showed various abilities to induce AP‐1 DNA binding. Mutation of cagA , cag PAI, or vacA , and the nonphosphorylateable CagA mutant ( cagA EPISA ) resulted in less H. pylori ‐induced AP‐1 DNA‐binding activity, while mutation of the H. pylori flagella had no effect. extracellular signal‐related kinase (ERK), p38, and c‐Jun N‐terminal kinase (JNK) each selectively regulated AP‐1 subcomponent expression and DNA‐binding activity. These results provide more insight into how H. pylori and MAPK modulate AP‐1 subcomponents in gastric epithelial cells to alter the expression of downstream target genes and affect cellular functions.