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

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 PLC gamma 2 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 PLC gamma 2 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 PLC gamma 2, while the effect of ghrelin is manifested by elevation in the membrane PLC gamma 2 activation and suppression in Rac1 translocation. However, blocking the LPS-induced Rac1 translocation, while detrimental to the PLC gamma 2 activation, has no effect on its membrane translocation. We reveal further that PLC gamma 2, 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 PLC gamma 2 phosphorylation on Ser. Thus, the results suggest that H. pylori-elicited increase in gastric mucosal PLC gamma 2 phosphorylation on Ser serves as an essential platform for Rac1 colocalization and amplification in PLC gamma 2 activation.