title: DGKζ is involved in LPS-activated phagocytosis through IQGAP1/Rac1 pathway.
abstract: Diacylglycerol kinase (DGK) plays an important role in phosphoinositide signaling cascade by regulating the intracellular level of diacylglycerol and phosphatidic acid. The DGK family is involved in various pathophysiological responses that are mediated through unique binding partners in different tissues and cells. In this study, we identified a small GTPase effector protein, IQGAP1, as a novel DGKζ-associated complex protein. A bacterial endotoxin, lipopolysaccharide (LPS), facilitated the complex formation in macrophages. Both proteins co-localized at the edge and phagocytic cup of the cell. Furthermore, RNA interference-mediated knockdown of DGKζ or IQGAP1 impaired LPS-induced Rac1 activation. Primary macrophages derived from DGKζ(-/-) mice attenuated LPS-induced phagocytosis of bacteria. These results suggest that DGKζ is involved in IQGAP1/Rac1-mediated phagocytosis upon LPS stimulation in macrophages.
authors.affiliation: Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585, Japan. m-okada@med.id.yamagata-u.ac.jp
authors.forename: Masashi
authors.initials: M
authors.lastname: Okada
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Hozumi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Iwazaki
authors.forename: Kentaro
authors.initials: K
authors.lastname: Misaki
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Yanagida
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Araki
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yagisawa
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Topham
authors.forename: Kozo
authors.initials: K
authors.lastname: Kaibuchi
authors.forename: Kaoru
authors.initials: K
authors.lastname: Goto
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019852:Diacylglycerol Kinase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000378:metabolism*; D010587:Phagocytosis; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
chemical_list: C101203:IQ motif containing GTPase activating protein 1; D008070:Lipopolysaccharides; D009479:Neuropeptides; C484602:Rac1 protein, mouse; D020703:ras GTPase-Activating Proteins; D019852:Diacylglycerol Kinase; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein