Regulation of ras exchange factors and cellular localization of ras activation by lipid messengers in T cells.
Regulation of ras exchange factors and cellular localization of ras activation by lipid messengers in T cells.
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DOI：
10.3389/fimmu.2013.00239
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发表时间：
2013-09-04
影响因子：
7.3
通讯作者：
Roose JP
中科院分区：
文献类型：
--
作者：
Jun JE;Rubio I;Roose JP
Ras-MAPK信号通路在整个进化过程中高度保守，并在广泛的受体刺激下游被激活。Ras鸟嘌呤核苷酸交换因子（Ras Guanine Nucleotide Exchange Factor，RasGEFs）催化Ras的GTP负载，在调节受体-配体诱导的Ras活性中发挥关键作用。在T细胞中，表达三个功能重要的RasGEF家族：RasGRF、RasGRP和Son of Sevenless（SOS）家族GEF。早期认识到Ras活化对于T细胞发育是关键的，并且RasGEF在其中发挥重要作用。最近的研究表明，Ras激活的细微差别似乎显着影响T细胞的发育和选择。这些细微差别包括模拟与数字Ras激活的不同生化模式，Ras激活的细胞定位差异，以及RasGEF在不同T细胞发育阶段之间的复杂相互作用，如各种新的小鼠模型所揭示的。在许多情况下，Ras激活中这些细微差别的确切性质或这些细微差别如何由RasGEFs的微调引起尚不清楚。一大组关键参与控制RasGEFs功能的生物分子是脂质第二信使。在T细胞受体（TCR）刺激后产生多种但不同的脂质产物，并与RasGRP和SOS RasGEF中的不同结构域结合，以促进膜锚定的Ras GTP酶的活化。在这篇综述中，我们强调了不同的脂质为基础的元素是如何产生的各种酶下游的TCR和其他受体，以及如何这些动态和相互关联的脂质产品可以微调Ras激活RasGEFs在发展中的T细胞。
The Ras-MAPK signaling pathway is highly conserved throughout evolution and is activated downstream of a wide range of receptor stimuli. Ras guanine nucleotide exchange factors (RasGEFs) catalyze GTP loading of Ras and play a pivotal role in regulating receptor-ligand induced Ras activity. In T cells, three families of functionally important RasGEFs are expressed: RasGRF, RasGRP, and Son of Sevenless (SOS)-family GEFs. Early on it was recognized that Ras activation is critical for T cell development and that the RasGEFs play an important role herein. More recent work has revealed that nuances in Ras activation appear to significantly impact T cell development and selection. These nuances include distinct biochemical patterns of analog versus digital Ras activation, differences in cellular localization of Ras activation, and intricate interplays between the RasGEFs during distinct T cell developmental stages as revealed by various new mouse models. In many instances, the exact nature of these nuances in Ras activation or how these may result from fine-tuning of the RasGEFs is not understood. One large group of biomolecules critically involved in the control of RasGEFs functions are lipid second messengers. Multiple, yet distinct lipid products are generated following T cell receptor (TCR) stimulation and bind to different domains in the RasGRP and SOS RasGEFs to facilitate the activation of the membrane-anchored Ras GTPases. In this review we highlight how different lipid-based elements are generated by various enzymes downstream of the TCR and other receptors and how these dynamic and interrelated lipid products may fine-tune Ras activation by RasGEFs in developing T cells.
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DOI：
10.1038/nrm3255
发表时间：
2011-12-22
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
56.9
作者：
Bashor, Caleb J.;Helman, Noah C.;Lim, Wendell A.
通讯作者：
Lim, Wendell A.
影响因子：
7.7
作者：
Augsten, M;Pusch, R;Rubio, I
通讯作者：
Rubio, I
影响因子：
5.3
作者：
Buchsbaum, RJ;Connolly, BA;Feig, LA
通讯作者：
Feig, LA
影响因子：
4.8
作者：
Caloca, Maria Jose;Delgado, Pilar;Bustelo, Xose R.
通讯作者：
Bustelo, Xose R.