磷酸脂酸调节 RA-GEFs 在趋化因子依赖的迁移中的亚细胞分布。
Phosphatidic acid regulates subcellular distribution of RA-GEFs critical for chemokine-dependent migration.
机构信息
Department of Biosciences, School of Science, Kitasato University, 1-15-1 Kitasato, Minamiku, Sagamihara, Kanagawa, 252-0337, Japan.
Department of Integrative Biology & Pharmacology, University of Texas Health Science at Houston 6431 Fannin St, Houston, TX, 77030, USA.
出版信息
Biochem Biophys Res Commun. 2020 Apr 2;524(2):325-331. doi: 10.1016/j.bbrc.2020.01.080. Epub 2020 Jan 26.
Integrin activation by Rap1-GTP is pivotal for lymphocyte trafficking. In this study, we show the phosphatidic acid (PA)-dependent membrane distribution of RA-GEF-1 and -2 (also known as Rapgef2 and 6), which are guanine nucleotide exchange factors for Rap1, plays important roles in lymphocyte migration. RA-GEF-1 associates with PA through 919-967 aa within CDC25 homology domain, and the deletion of this region of RA-GEF-1 inhibits chemokine-dependent migration. Chemokine stimulation induces temporal production of PA on the plasma membrane, which is not necessary for Rap1 activation, but the translocation of RA-GEFs. Thus, chemokine-dependent generation of PA is critical for lymphocyte migration through membrane localization of RA-GEFs.
Rap1-GTP 对整合素的激活对于淋巴细胞的迁移至关重要。在这项研究中，我们展示了磷酸脂酸（PA）对 RA-GEF-1 和 -2（也称为 Rapgef2 和 6）的膜分布的依赖性，它们是 Rap1 的鸟嘌呤核苷酸交换因子，在淋巴细胞迁移中发挥重要作用。RA-GEF-1 通过 CDC25 同源域内的 919-967 aa 与 PA 结合，并且 RA-GEF-1 的该区域的缺失抑制趋化因子依赖性迁移。趋化因子刺激诱导质膜上 PA 的时间依赖性产生，这对于 Rap1 激活不是必需的，但对于 RA-GEFs 的易位是必需的。因此，通过 RA-GEFs 的膜定位，趋化因子依赖性生成的 PA 对于淋巴细胞迁移是至关重要的。
Zotero 插件