Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
Biochem Biophys Res Commun. 2012 Apr 6;420(2):479-84. doi: 10.1016/j.bbrc.2012.03.057. Epub 2012 Mar 17.
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.
二酰基甘油激酶（DGK）通过调节细胞内二酰基甘油和磷脂酸的水平，在磷酸肌醇信号级联中发挥重要作用。DGK 家族参与各种病理生理反应，这些反应通过不同组织和细胞中的独特结合伴侣介导。在这项研究中，我们鉴定了一种小 GTP 酶效应蛋白 IQGAP1，作为一种新型的 DGKζ 相关复合物蛋白。细菌内毒素脂多糖（LPS）促进了巨噬细胞中复合物的形成。这两种蛋白在细胞的边缘和吞噬杯中共定位。此外，RNA 干扰介导的 DGKζ 或 IQGAP1 敲低削弱了 LPS 诱导的 Rac1 激活。来自 DGKζ（-/-）小鼠的原代巨噬细胞减弱了 LPS 诱导的细菌吞噬作用。这些结果表明，DGKζ 参与 LPS 刺激巨噬细胞中 IQGAP1/Rac1 介导的吞噬作用。
