权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

T Cell Receptor Signaling by Phosphorylated Forms of TCR

TCR 磷酸化形式的 T 细胞受体信号传导

基本信息

批准号：
7472298
负责人：
NICOLAI Stanislas Cyrille VAN OERS
金额：
$ 29.02万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-03-01 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7472298
关键词：
3-Dimensional Accounting Amino Acid Sequence Autoimmune Diseases Autoimmune Process Bacterial Infections Binding Biochemical Biological Assay CD3 Antigens CDKN1A gene Cell Survival Cell membrane Cell physiology Complex Development Engineering Failure Family Image Immune Immune response Immune system Immunity Infection Lead Life Ligand Binding Ligands Listeria Lymphocyte Lymphocyte Function Membrane Microdomains Minor Molecular Monitor Motion Mus Mutation P23 Peripheral Phosphoric Monoester Hydrolases Phosphorylation Phosphotransferases Population Process Property Protein Tyrosine Kinase Protein Tyrosine Phosphatase Protein-Serine-Threonine Kinases Proteins Receptor Signaling Research Personnel Role Series Signal Transduction Signaling Protein T-Cell Development T-Cell Receptor T-Lymphocyte Techniques Therapeutic Transgenic Mice Transgenic Organisms Translating Tumor Suppression Tyrosine Tyrosine Phosphorylation Site Viral Virus Diseases base immune function immunological synapse insight molecular mass oncoprotein p21 pathogen programs receptor receptor function response selective expression synaptogenesis transmission process

项目摘要

DESCRIPTION (provided by applicant): T cells are an essential component of the immune system, recognizing the presence of foreign pathogens and setting in motion very specific intracellular responses to protect the body from serious infection. The T cell receptor (TCR) complex controls these T cell processes. It discriminates very subtle differences in the foreign molecules that it binds to, responding by activating the appropriate intracellular signals that will lead to an effective immune response. The underlying objective of this application is to understand exactly how the T cell receptor controls T cell development and immune functions. This is critical because failure to activate an appropriate response leads to serious infections and inappropriate activation leads to autoimmune diseases. This proposal focuses on the role of the TCRzeta subunit, and the deceptively simple phosphorylation of specific tyrosine residues that is at the core of the TCR's ability to regulate T cell development and immune functions. The TCRzeta subunit forms two discrete tyrosine phosphorylated forms of 21 and 23 kDa (p21 and p23). Preliminary results using a series of transgenic mice that differentially express these phosphorylated proteins indicate that p21 and p23 possess essential non-redundant functions in controlling T cell development, survival, and functions during infections. There are four specific aims in this proposal. The first is to identify the molecular mechanism(s) responsible for the different functions of p21 and p23. The second involves delineating the contribution of p21 to T cell survival. In the third, the functional contribution of phosphorylated zeta to T cells during immune responses to bacterial infections will be determined. The forth aim involves a characterization of phosphatases and kinases that regulate TCR functions. The approaches will incorporate sophisticated biochemical and 3-d imaging studies with the various TCRzeta transgenic lines. The studies will include immunological assays to monitor lymphocyte functions during normal lymphocyte development as well as during infections and autoimmune scenarios.

描述(申请人提供)：T细胞是免疫系统的重要组成部分，识别外来病原体的存在，并启动非常特定的细胞内反应，以保护身体免受严重感染。T细胞受体(TCR)复合体控制这些T细胞过程。它能区分与其结合的外来分子中非常细微的差异，通过激活适当的细胞内信号来做出反应，这将导致有效的免疫反应。这项应用的基本目标是确切地了解T细胞受体如何控制T细胞的发育和免疫功能。这一点至关重要，因为未能激活适当的反应会导致严重的感染，而不适当的激活会导致自身免疫性疾病。这项建议的重点是TCRzeta亚单位的作用，以及特定酪氨酸残基的简单磷酸化，这是TCR调节T细胞发育和免疫功能的核心。TCRzeta亚基形成两种不同的酪氨酸磷酸化形式，分别为21和23 kDa(p21和p23)。利用一系列差异表达这些磷酸化蛋白的转基因小鼠的初步结果表明，p21和p23在控制T细胞的发育、存活和感染期间的功能方面具有基本的非冗余功能。这项提议有四个具体目标。首先是确定p21和p23不同功能的分子机制(S)。第二个涉及描绘p21对T细胞存活的贡献。在第三项研究中，将确定在细菌感染的免疫反应中，磷酸化Zeta对T细胞的功能贡献。第四个目标涉及调节TCR功能的磷酸酶和激酶的特征。这些方法将结合各种TCRzeta转基因品系的复杂生化和3-d成像研究。这些研究将包括免疫分析，以监测正常淋巴细胞发育期间以及感染和自身免疫情况下的淋巴细胞功能。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

T cell receptor-mediated signs and signals governing T cell development.

T 细胞受体介导的控制 T 细胞发育的体征和信号。

DOI：
10.1006/smim.1999.0179
发表时间：
1999
期刊：
Seminars in immunology.
影响因子：
0
作者：
vanOers,NS
通讯作者：
vanOers,NS

The cytoplasmic tail of the T cell receptor CD3 epsilon subunit contains a phospholipid-binding motif that regulates T cell functions.

DOI：
10.4049/jimmunol.0900404
发表时间：
2009-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
0
作者：
Deford-Watts LM;Tassin TC;Becker AM;Medeiros JJ;Albanesi JP;Love PE;Wülfing C;van Oers NS
通讯作者：
van Oers NS

Dynamic modulation of thymic microRNAs in response to stress.

DOI：
10.1371/journal.pone.0027580
发表时间：
2011
期刊：
PloS one
影响因子：
3.7
作者：
Belkaya S;Silge RL;Hoover AR;Medeiros JJ;Eitson JL;Becker AM;de la Morena MT;Bassel-Duby RS;van Oers NS
通讯作者：
van Oers NS

The CD3 zeta subunit contains a phosphoinositide-binding motif that is required for the stable accumulation of TCR-CD3 complex at the immunological synapse.

DOI：
10.4049/jimmunol.1002721
发表时间：
2011-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
0
作者：
DeFord-Watts LM;Dougall DS;Belkaya S;Johnson BA;Eitson JL;Roybal KT;Barylko B;Albanesi JP;Wülfing C;van Oers NS
通讯作者：
van Oers NS

Positive selection by the pre-TCR yields mature CD8+ T cells.

前 TCR 的阳性选择产生成熟的 CD8 T 细胞。

DOI：
10.4049/jimmunol.169.9.4913
发表时间：
2002
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
0
作者：
Ito,Yuriko;Arai,Satoko;vanOers,NicolaiSC;Aifantis,Iannis;vonBoehmer,Harald;Miyazaki,Toru
通讯作者：
Miyazaki,Toru