GTP-BINDING PROTEIN RHO IN T CELL SIGNALING PATHWAYS
T 细胞信号通路中的 GTP 结合蛋白 RHO
基本信息
- 批准号:6168984
- 负责人:
- 金额:$ 2.71万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-07-01 至 2000-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Having been clinically trained in Internal Medicine and Infectious
Diseases. I have long been intrigued by the biological responses
to disease. My interest in Infectious Diseases and the basic
processes that govern immune responses led me to the study of
signal transduction pathways in leukocytes. Over the last several
years. I have devoted the majority of my time to developing an
understanding of the molecular biology and biochemistry of
lymphocyte signalling and particularly the importance of small G
proteins in this process. Building upon this foundation, my goal is
to make the transition from a postdoctoral researcher to an
independent investigator with an expertise in basic signal
transduction in leukocytes. The T cell receptor complex (TCR)
mediated signalling processes that are necessary for activation and
proliferation of lymphocytes during immune responses. Ligation
of the TCR by antigenic stimuli drives cellular responses that
include upregulation of cytokine gene expression, and, ultimately,
T cell activation. In addition, ligation of the TCR leads to
remodeling of the action cytoskeleton; interactions between the
TCR and this action cytoskeleton are crucial for effective T cell
activation. Members of the Rho subfamily of GTPases are likely
candidates to function as regulators of TCR-mediated signal
transduction pathways. The role of Rho in lymphocytes, however,
has received little attention. Studies in other systems suggest that
Rho likely coordinates intracellular signalling pathways regulating
both cytoskeletal remodeling and protein kinase-activated gene
expression. The overall objective of this work is to investigate the
hypothesis that Rho proteins coordinate such dual signal
transduction pathways in lymphocytes, specifically those pathways
emerging from TCR engagement and leading to effective T cell
activation. Our study aims will be to 1) establish the role of Rho
during classic T cell activation pathways, and to 2) characterize
the function of Rho in the interaction between the TCR and early
signalling events occurring at the plasma membrane. Using a
transient expression system based on Sindbis virus we will express
Rho proteins, including constitutively active and dominant
negative mutants. Inlyphocytes; in addition, we will express C3
exoenzyme a specific inhibitor of Rho function. These tools will
allow us to carefully delineate the role of Rho during T cell
activation as assessed by both downstream cytokine gene
expression and by alterations in early TCR signalling events at the
plasma membrane. The environment in which I will complete this
project is ideal. Experts in the areas of immunology. G protein
signalling and protein biochemistry are committed to my efforts
and will provide a rigorous academic milieu in which I can
develop my skills effectively. Advocates within the Beirne Carter
Center for Immunology and the Departments of Medicine and
Microbiology will insure that I receive excellent training as I make
the transition to an independent investigator.
接受过内科和感染科的临床培训
疾病 我一直对生物反应很感兴趣
疾病。 我对传染病的兴趣
控制免疫反应的过程使我开始研究
白细胞中的信号转导途径。 过去几
年 我把大部分时间都花在了开发
分子生物学和生物化学的理解,
淋巴细胞信号传导,特别是小G蛋白的重要性
蛋白质在这个过程中 在此基础上,我的目标是
从一个博士后研究员到一个
具有基本信号专业知识的独立调查员
白细胞中的转导。 T细胞受体复合物(TCR)
介导的信号传导过程是激活所必需的,
淋巴细胞在免疫反应中的增殖。 结扎
抗原性刺激对TCR的影响驱动细胞反应,
包括细胞因子基因表达上调,最终,
T细胞活化。 此外,TCR的连接导致
重塑的行动细胞骨架;之间的相互作用
TCR及其作用细胞骨架对有效的T细胞免疫至关重要。
activation. GTP酶的Rho亚家族成员可能是
作为TCR介导的信号调节剂的候选物
转导途径。 然而,Rho在淋巴细胞中的作用,
很少受到关注。 对其他系统的研究表明,
Rho可能协调细胞内信号传导途径,
细胞骨架重塑和蛋白激酶激活基因
表情这项工作的总体目标是调查
Rho蛋白协调这种双重信号假说
淋巴细胞中的转导途径,特别是那些
从TCR接合中出现,并导致有效的T细胞
activation. 我们的研究目标是:1)确定Rho的作用
在经典的T细胞活化途径,并2)表征
Rho在TCR与早期T细胞相互作用中的作用
发生在质膜上的信号事件。 使用
基于辛德毕斯病毒的瞬时表达系统,我们将表达
Rho蛋白,包括组成型活性和显性
阴性突变体 此外,我们还将表达C3
外切酶是Rho功能的特异性抑制剂。这些工具将
这使我们能够仔细描述Rho在T细胞增殖过程中的作用,
通过两种下游细胞因子基因评估的激活
表达和早期TCR信号事件的改变,
质膜 我将在其中完成这件事的环境
项目是理想的。 免疫学领域的专家。 G蛋白
信号传导和蛋白质生物化学致力于
并将提供一个严格的学术环境,
有效地发展我的技能。 Beirne Carter的律师
免疫学中心和医学系,
微生物学将确保我得到良好的培训,因为我使
向独立调查员的过渡
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JONATHAN P MOORMAN其他文献
JONATHAN P MOORMAN的其他文献
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The role of microRNAs in premature T cell aging during HIV infection
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GTP-BINDING PROTEIN RHO IN T CELL SIGNALING PATHWAYS
T 细胞信号通路中的 GTP 结合蛋白 RHO
- 批准号:
2886071 - 财政年份:1997
- 资助金额:
$ 2.71万 - 项目类别:
GTP-BINDING PROTEIN RHO IN T CELL SIGNALING PATHWAYS
T 细胞信号通路中的 GTP 结合蛋白 RHO
- 批准号:
2671469 - 财政年份:1997
- 资助金额:
$ 2.71万 - 项目类别:
GTP-BINDING PROTEIN RHO IN T CELL SIGNALING PATHWAYS
T 细胞信号通路中的 GTP 结合蛋白 RHO
- 批准号:
2384407 - 财政年份:1997
- 资助金额:
$ 2.71万 - 项目类别:
GTP-BINDING PROTEIN RHO IN T CELL SIGNALING PATHWAYS
T 细胞信号通路中的 GTP 结合蛋白 RHO
- 批准号:
6409615 - 财政年份:1997
- 资助金额:
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