Premium
Epidermal growth factor (EGF) induced inhibition of acid secretion by functional translocation of ezrin
Author(s) -
Delaney Joseph,
Zhou Rihong,
Mettler Shelley,
Forte John G.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb21-a
Subject(s) - ezrin , epidermal growth factor , microbiology and biotechnology , parietal cell , secretion , phosphorylation , radixin , histamine , biology , chemistry , gastric acid , cell , biochemistry , endocrinology , cytoskeleton , receptor
EGF has been shown to inhibit gastric acid secretion. In isolated gastric glands EGF inhibits acid secretion at sub‐maximal level of stimulation by histamine, and this inhibition is attenuated as glands are maximally stimulated via the histamine/cAMP pathway, suggesting there may be antagonism between the cAMP pathway to stimulate acid secretion and the EGF pathway for cell regulation. EGF may act through the membrane cytoskeletal linker ezrin, a member of the Ezrin/Radixin/Moesin (ERM) family, through phosphorylation of threonine 567. Phosphorylation of T567 reportedly helps in the activation of ezrin. However, our previous studies showed a T567D mutant to localize basolaterally and cause misdirected microvilli formation, inhibiting acid secretion. Here we explore how high [EGF] (150ng/mL) interferes with the acid secretory pathway. Immunostaining of non‐secreting parietal cells incubated with EGF showed increased ezrin staining in lamellipodia and filopodia, compared to cells cultured without EGF. Also, when treated with histamine EGF cells demonstrated reduced stimulation, especially when the cell had numerous ezrin‐filled projections. Stronger stimulation with both histamine and IBMX overrode this inhibition. Immunoprecipitation assays where anti‐phospho T567 ezrin antibodies were bound to beads revealed that only a small % of total ezrin is T567‐phosphorylated in the parietal cell. Since EGF‐treated parietal cells have extensive lamellipodia and filopodia, reminiscent of the T567D mutant, we propose EGF inhibits parietal cell secretion in via ezrin phosphorylation at T567 and translocation and activation of ezrin to form basolateral protrusions, thus challenging the cAMP directed recruitment of acid secretory resources at the apical membrane.