Phosphoinositide-specific phospholipase C (PLC) enzymes are crucial elements of signal transduction pathways that provide a common link of communication integrating specific receptor responses to a variety of hormones, growth factors, and bacterial endotoxins with the intended intracellular targets. Here, we examined the involvement of PLC in modulation of gastric mucosal inflammatory responses to Helicobacter pylori LPS by peptide hormone, ghrelin. We show that stimulation of gastric mucosal cells with the LPS leads to the activation and membrane translocation of the γ2 isoform of PLC, phosphorylated on Tyr as well as Ser, while the effect of ghrelin is reflected in the translocation and phosphorylation of membrane-associated PLCγ2 on Tyr mainly. Moreover, we demonstrate that PLCγ2 phosphorylation on Tyr remains under the control of the Src family protein tyrosine kinases (SFK-PTKs), and is intimately linked to PLCγ2 membrane localization, while the LPS-induced phosphorylation of membrane-recruited PLCγ2 on Ser displays dependence on protein kinase Cδ (PKCδ) and leads to the amplification in PLCγ2 activation. Thus, our findings link the extent of H. pylori-elicited gastric mucosal inflammatory involvement to the PKCδ-mediated amplification in PLCγ2 activation through phosphorylation on Ser.