<i>Porphyromonas gingivalis</i>-Induced GEF Dock180 Activation by Src/PKC<i>δ</i>-Dependent Phosphorylation Mediates PLC<i>γ</i>2 Amplification in Salivary Gland Acinar Cells: Modulatory Effect of Ghrelin

• 作者: Amalia Slomiany Bronislaw L. Slomiany
• 来源期刊: 生物科学与医学(英文)
• 学科: 医学
• 关键词: P. gingivalis Salivary Acinar Cell GHRELIN Dock180 Phosphorylation SRC PKCδ PLCγ2 ACTIVATION
• 年，卷（期）: 2015,（7）
• 页码范围: 66-77
• 页数: 12页
• 分类号: R73

摘要

Phospholipase Cγ2 (PLCγ2) plays a pivotal role in mediation of inflammatory reaction to bacterial lipopolysaccharide (LPS) as well as serves as a key target in modulatory influence of the hormone ghrelin. Here we explore the involvement of Rac1 and its activator, guanine nucleotide exchange factor (GEF), Dock180, in mediation of PLCγ2 activation in salivary gland acinar cells in response to P. gingivalis LPS and ghrelin. We show that stimulation of the acinar cells with the LPS leads to up-regulation in Dock and PLCγ2 activation, and is reflected in the membrane translocation of Rac1 and PLCγ2, while the effect of ghrelin is manifested by the suppression in Rac1 translocation. Further, we reveal that stimulation with the LPS leads to Dock180 phosphorylation on Tyr and Ser, while the modulatory influence of ghrelin, manifested by a drop in membrane Rac1-GTP, is asso-ciated with a distinct decrease in Dock180 phosphorylation on Ser. Moreover, we demonstrate that phosphorylation on Tyr remains under the control of Src kinase and is accompanied by Dock180 membrane translocation, while protein kinase Cδ(PKCδ) is involved in the LPS-induced phosphorylation of the membrane-recruited Dock180 on Ser. Thus, our findings underscore the role of Src/PKCδ-mediated GEF Dock180 phosphorylation on Tyr/Ser in modulation of salivary gland acinar cell PLCγ2 activation in response to P. gingivalis as well as ghrelin.