title: Mechanism of Rac1-induced amplification in gastric mucosal phospholipase Cγ2 activation in response to Helicobacter pylori: modulatory effect of ghrelin.
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, the results suggest that H. pylori-elicited increase in gastric mucosal PLCγ2 phosphorylation on Ser serves as an essential platform for Rac1 colocalization and amplification in PLCγ2 activation.
authors: Research Center C875, Rutgers School of Dental Medicine Rutgers, The State University of New Jersey, 110 Bergen Street, PO Box 1709, Newark, NJ, 07103-2400, USA, slomiabr@sdm.rutgers.edu.
authors: B L
authors: BL
authors: Slomiany
authors: A
authors: A
authors: Slomiany
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D054439:Ghrelin / Q000378:metabolism*; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051966:Phospholipase C gamma / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D054439:Ghrelin; D008070:Lipopolysaccharides; C442865:lipopolysaccharide, Helicobacter pylori; D051966:Phospholipase C gamma; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein