Vigorito Elena, Billadeu Daniel D, Savoy Doris, McAdam Simon, Doody Gina, Fort Phillipe, Turner Martin
Laboratory for Lymphocyte Signalling and Development, Molecular Immunology Programme, The Babraham Institute, Cambridge, UK.
Oncogene. 2003 Jan 23;22(3):330-42. doi: 10.1038/sj.onc.1206116.
RhoG, a member of the Rho family of GTPases, has been implicated as a regulator of the actin cytoskeleton. In this study, we show a novel function for the small GTPase RhoG on the regulation of the interferon-gamma promoter and nuclear factor of activated T cells (NFAT) gene transcription in lymphocytes. Optimal function of RhoG for the expression of these genes requires a calcium signal, normally provided by the antigen receptor. In addition, RhoG potentiation of NFAT requires the indirect activity of Rac and Cdc42; however, pathways distinct from those activated by Rac and Cdc42 mediate RhoG activation of NFAT-dependent transcription. Using effector domain mutants of RhoG we found that its ability to potentiate NFAT-dependent transcription correlates with its capacity to increase actin polymerization, supporting the suggestion that NFAT-dependent transcription is an actin-dependent process. RhoG also promotes T-cell spreading on fibronectin, a property that is independent of its ability to enhance NFAT-dependent transcription. Hence, these results implicate RhoG in leukocyte trafficking and the control of gene expression induced in response to antigen encounter.
RhoG是GTP酶Rho家族的成员之一，被认为是肌动蛋白细胞骨架的调节因子。在本研究中，我们展示了小GTP酶RhoG在淋巴细胞中对干扰素-γ启动子和活化T细胞核因子（NFAT）基因转录调控方面的新功能。RhoG对这些基因表达的最佳功能需要钙信号，通常由抗原受体提供。此外，RhoG对NFAT的增强作用需要Rac和Cdc42的间接活性；然而，不同于Rac和Cdc42激活的途径介导了RhoG对NFAT依赖性转录的激活。使用RhoG的效应器结构域突变体，我们发现其增强NFAT依赖性转录的能力与其增加肌动蛋白聚合的能力相关，这支持了NFAT依赖性转录是一个肌动蛋白依赖性过程的观点。RhoG还促进T细胞在纤连蛋白上的铺展，这一特性与其增强NFAT依赖性转录的能力无关。因此，这些结果表明RhoG参与白细胞运输以及对抗原接触诱导的基因表达的控制。
