Inflammopharmacology

, Volume 22, Issue 4, pp 251–262 | Cite as

Modulation of gastric mucosal inflammatory responses to Helicobacter pylori via ghrelin-induced protein kinase Cδ tyrosine phosphorylation

Research Article

Abstract

A peptide hormone, ghrelin, plays a key role in modulation of gastric mucosal inflammatory responses to Helicobacter pylori by controlling the activation of constitutive nitric oxide synthase via Src/Akt-dependent phosphorylation that requires phosphatidylinositol 3-kinase (PI3K) participation. Here, we examined the relationship among PI3K; its upstream effector, protein kinase C (PKC); and cSrc. We show that stimulation of gastric mucosal cells with H. pylori LPS leads to the activation and membrane translocation of Ser-phosphorylated PKCδ, while the effect of ghrelin is reflected in the phosphorylation of membrane-associated PKCδ on Tyr. Further, we demonstrate that in response to the LPS-induced PKCδ activation both PI3K and Src show a marked increase in their Ser phosphorylation, while the effect of ghrelin is manifested in the phosphorylation of PI3K and cSrc at Tyr. Moreover, whereas Tyr phosphorylation of PKCδ exhibited susceptibility to cSrc inhibitor (PP2), the inhibitor of PKC (GF109203X) but not that of cSrc (PP2) blocked the Tyr phosphorylation of PI3K, while ghrelin-induced cSrc phosphorylation at Tyr was subject to inhibition by the inhibitors of PKC and PI3K. Thus, our findings stipulate the prerequisite of PKCδ in the activation of PI3K as well as cSrc, and imply that PI3K activation provides an essential platform for ghrelin-induced cSrc activation through autophosphorylation at Tyr416. We also reveal that ghrelin-elicited up-regulation in PKCδ activation by Tyr phosphorylation shows dependence on cSrc activity.

Keywords

Helicobacter pylori Gastric mucosa Ghrelin PKCδ activation PI3K cSrc 

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Copyright information

© Springer Basel 2014

Authors and Affiliations

  1. 1.Research Center, C875, Rutgers School of Dental MedicineRutgers, The State University of New JerseyNewarkUSA

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