The role of the RasGRP protein family in lymphocyte development

RasGRP 蛋白家族在淋巴细胞发育中的作用

• 批准号: 418161-2012
• 负责人: Baldwin, Troy
• 金额: $ 2.04万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=551268
• 关键词: role; RasGRP; protein; family; lymphocyte

T cells are a population of white blood cells that patrol the body in search of invading microorganisms. During their development in an organ called the thymus, T cells mature through a well-defined and easily monitored series of stages culminating with their entry into the circulation. Because the pathway of T cell development is well-known, it is often used as a model system with which to understand the function and regulation of various signaling pathways that are crucial to many biological responses including growth, differentiation, survival and death. This research program focuses on understanding the regulation of a critically important signaling pathway called the Ras/MAPK pathway by a family of proteins, collectively called the RasGRP family, using early T cell development as a model system. In T cells and many other blood cells, two families of proteins are thought to activate the Ras/MAPK pathway; the RasGRP and the Sos families. While it is known that the Ras/MAPK pathway is activated during early T cell development, the contribution of RasGRP proteins and Sos proteins to Ras activation is unclear. Using cell culture with various inhibitors and mice deficient in RasGRP proteins, we will determine the interplay between RasGRPs and Sos at various stages of T cell development. Furthermore, we will examine the mechanisms by which the RasGRP proteins are regulated by expressing mutant RasGRP proteins in cells that are genetically deficient for RasGRPs. Collectively, these studies will shed light on to the regulation of Ras by RasGRP and Sos proteins in T cells that can be applied to other cell types and biological responses.

T细胞是巡逻人体以寻找入侵微生物的白细胞群体。在称为胸腺的器官中发育过程中，T细胞通过定义明确且易于监测的一系列阶段成熟，最终进入循环。由于T细胞发育的途径是众所周知的，因此通常将其用作模型系统，用于了解各种信号通路的功能和调控，这些途径对于许多生物学反应至关重要，包括生长，分化，生存和死亡。该研究计划的重点是理解一个非常重要的信号通路，该蛋白质统称为蛋白质，称为RAS/MAPK途径，共同称为RASGRP家族，使用早期T细胞开发作为模型系统。在T细胞和许多其他血细胞中，两个蛋白质家族被认为可以激活RAS/MAPK途径。 Rasgrp和SOS家族。虽然众所周知，RAS/MAPK途径在早期T细胞发育过程中被激活，但RASGRP蛋白和SOS蛋白对RAS激活的贡献尚不清楚。在T细胞发育的各个阶段，使用缺乏RASGRP蛋白质的各种抑制剂和小鼠的细胞培养，我们将确定RASGRPS和SOS之间的相互作用。此外，我们将检查通过在遗传上缺乏RASGRP的细胞中表达突变体RASGRP蛋白来调节RASGRP蛋白的机制。总的来说，这些研究将阐明可用于其他细胞类型和生物学反应的T细胞中RASGRP和SOS蛋白对RAS的调节。