title: Role of protein kinase D2 phosphorylation on Tyr in modulation by ghrelin of Helicobacter pylori-induced up-regulation in gastric mucosal matrix metalloproteinase-9 (MMP-9) secretion.
abstract: Matrix metalloproteinas-9 (MMP-9) is a glycosylated endopeptidase associated with host reaction to microbial endotoxins and also characterizes gastric mucosal inflammatory response to H. pylori infection. Here, we report on the factors involved in gastric mucosal MMP-9 secretion in response to H. pylori LPS, and the effect of hormone, ghrelin. We show that both the LPS-elicited induction in MMP-9 secretion and also the modulatory influence of ghrelin occur at the level of MMP-9 processing between the endoplasmic reticulum (ER) and Golgi. Further, we demonstrate that the LPS effect is associated with up-regulation in the activation of Arf1, a small GTPase of the ADP-ribosylation factor family, and the recruitment and phosphorylation of protein kinase D2 (PKD2), involved in the secretory cargo processing in the Golgi. Moreover, we reveal that the LPS-induced up-regulation in MMP-9 secretion is reflected in a marked increase in PKCδ-mediated PKD2 phosphorylation on Ser, while the modulatory effect of ghrelin is manifested by the SFK-PTKs-dependent phosphorylation of PKD2 on Tyr. Thus, our findings demonstrate the role of Arf1/PKD2 in mediation of H. pylori LPS-induced up-regulation in gastric mucosal MMP-9 secretion and suggest the modulatory mechanism of ghrelin action.
authors.affiliation: Research Center, 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.forename: B L
authors.initials: BL
authors.lastname: Slomiany
authors.affiliation: Research Center, Rutgers School of Dental Medicine, Rutgers, The State University of New Jersey, 110 Bergen Street, PO Box 1709, Newark, NJ, 07103-2400, USA.
authors.forename: A
authors.initials: A
authors.lastname: Slomiany
mesh_terms: D000818:Animals; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D054439:Ghrelin / Q000494:pharmacology*; D016480:Helicobacter pylori; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D000091283:Protein Kinase D2; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D014443:Tyrosine / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D054439:Ghrelin; D000091283:Protein Kinase D2; D014443:Tyrosine; D011494:Protein Kinases; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: Arf1; Gastric mucosa; Ghrelin; H. pylori LPS; MMP-9; PKD2 Tyr/Ser phosphorylation