CHARACTERIZATION OF TROPOMYOSIN-RELATED RECEPTOR KINASE A (TRKA) SIGNALING

原肌球蛋白相关受体激酶 A (TRKA) 信号转导的表征

• 批准号: 8363821
• 负责人: ALMA L BURLINGAME
• 金额: $ 3.99万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363821
• 关键词: Affinity; Docking; Engineering; Funding; Grant; Label; Mass Spectrum Analysis; Modification; NGFR Protein; National Center for Research Resources; Nerve Growth Factors; Neurons; Peripheral; Phosphorylation; Phosphotransferases; Phosphotyrosine; Platelet-Derived Growth Factor Receptor; Principal Investigator; Proteins; Receptor Protein-Tyrosine Kinases; Research; Research Infrastructure; Resources; Role; Sensory; Signal Pathway; Signal Transduction; Signaling Molecule; Site; Source; Tropomyosin; Tyrosine; Tyrosine Kinase Domain; United States National Institutes of Health; analog; cost; extracellular; interest; mutant; receptor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Nerve growth factor (NGF) is a signaling molecule, originally discovered for its role on differentiation and survival of peripheral sensory and sympathetic neurons. The activation of the receptor tyrosine kinase, TrkA, by the NGF leads to the phosphorylation of several tyrosines in the intracellular part of the receptor. Two phosphotyrosines located at 490 and 785 create docking sites for adaptator or effector proteins which stimulate several signaling pathways. My research interest is focused in characterizing the phosphoproteome specifically activated by these 2 phosphotyrosines by using mutant receptors. Moreover, the use of a chimeric receptor (extracellular part of the PDGF receptor/intracellular part of TrkA) allows the identification of the signaling pathways specific of TrkA and not of p75NTR. I am also interested in characterizing the direct substrates of the tyrosine kinase domain of TrkA. The kinase engineered to use synthetic ATP analogs specifically thiophosphorylates its substrates. This thiophosphorylation modification provides a tag that can be used to affinity purify and identify labeled proteins. This project will further understanding of the function of the NGF receptor in neurons.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 神经生长因子 (NGF) 是一种信号分子，最初因其在外周感觉和交感神经元的分化和存活中的作用而被发现。 NGF 对受体酪氨酸激酶 TrkA 的激活导致受体细胞内部分的几个酪氨酸磷酸化。位于 490 和 785 的两个磷酸酪氨酸为适配器或效应蛋白创建对接位点，刺激多种信号传导途径。我的研究兴趣集中在通过使用突变受体来表征由这 2 种磷酸酪氨酸特异性激活的磷酸蛋白质组。此外，嵌合受体（PDGF受体的细胞外部分/TrkA的细胞内部分）的使用允许鉴定TrkA特异的信号传导途径，而不是p75NTR特异的信号传导途径。 我还对表征 TrkA 酪氨酸激酶结构域的直接底物感兴趣。该激酶被设计为使用合成 ATP 类似物特异性地硫代磷酸化其底物。这种硫代磷酸化修饰提供了可用于亲和纯化和鉴定标记蛋白质的标签。该项目将进一步了解神经元中 NGF 受体的功能。