Mechanism of Rac1-induced amplification in gastric mucosal phospholipase Cγ2 activation in response to Helicobacter pylori: modulatory effect of ghrelin

Inflammopharmacology
Bronislaw L Slomiany, Amalia Slomiany

Abstract

Membrane recruitment followed by targeted phosphorylation of specific Tyr and Ser residues and the interaction with Rac GTPases are the crucial parts of an elaborate mechanism of PLCγ2 activation essential for its role in linking the specific receptor responses to a variety of hormones and bacterial endotoxins with the intended intracellular targets. Here, we explored the involvement of Rac in mediation of PLCγ2 activation associated with gastric mucosal inflammatory responses to H. pylori LPS and the hormone, ghrelin. We show that stimulation of gastric mucosal cells with the LPS leads to the membrane translocation of Rac1 as well as PLCγ2, while the effect of ghrelin is manifested by elevation in the membrane PLCγ2 activation and suppression in Rac1 translocation. However, blocking the LPS-induced Rac1 translocation, while detrimental to the PLCγ2 activation, has no effect on its membrane translocation. We reveal further that PLCγ2, localized in the membrane in association with Rac1 following the LPS stimulation, exhibits a marked increase in phosphorylation on Ser, while the modulatory effect of ghrelin, manifested by a drop in Rac1 translocation, is associated with a distinct decrease in PLCγ2 phosphorylation on Ser. Thus, ...Continue Reading

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Citations

Jul 15, 2017·Journal of Pharmacology & Pharmacotherapeutics·Sahoo AshokkumarVikram Kate
Jul 31, 2018·Journal of Immunology Research·Liqian ZhuGaiping Zhang

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