Regulation Of Crosstalk Between Trk and p75 NTR

Trk 和 p75 NTR 之间串扰的调节

• 批准号: 6559430
• 负责人: MICHAEL J CHUMLEY
• 金额: $ 4.42万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6559430
• 关键词: Retroviridae; biological signal transduction; ceramides; developmental genetics; enzyme activity; gene mutation; growth factor receptors; neurogenetics; neurotrophic factors; phosphatidylinositol 3 kinase; receptor expression; sphingomyelin phosphodiesterase; tissue /cell culture; transfection /expression vector

DESCRIPTION (provided by applicant): The high-affinity Trk and low-affinity p75NTR receptors play critical roles in the growth, differentiation, and survival or neurons and glial cells. Numerous reports support a cross talk between these neurotrophin signaling pathways that is likely critical in regulation of growth, differentiation, and survival. Furthermore, this interplay of signaling pathways likely requires a high degree of organization for optimal regulation. Therefore, the long-term objectives of this research are to define the molecular mechanisms that regulate cross talk between Trk A and p75NTR neurotrophin receptors and the functional significance of this cross talk in neuronal populations. Data presented herein strongly suggest that the Trk A and p75NTR pathways converge at the interaction of PI 3-kinase and acid sphingomyelinase (SMase). However, it remains unknown how PI 3-kinase interacts with acid SMase, Thus, the Specific Aims of this proposal are: 1) to determine the minimal binding domain within p85 that interacts with acid SMase an 2) to assess the role of the YXXM, NPXY, and proline-rich sequences of acid SMase in the interaction with p85.

描述（由申请人提供）：高亲和力TRK和低亲和力 P75NTR受体在增长，分化和 生存或神经元和神经胶质细胞。许多报告支持串口 在这些神经营养蛋白信号通路之间可能至关重要的 调节生长，分化和生存。此外，这个 信号通路的相互作用可能需要高度的组织 用于最佳调节。因此，这项研究的长期目标 是定义调节trk a之间交叉谈话的分子机制 和p75NTR神经营养蛋白受体以及该十字的功能意义 在神经元种群中谈论。本文提供的数据强烈表明 TRK A和P75NTR途径在PI 3-激酶与酸的相互作用上收敛 鞘磷脂酶（SMASE）。但是，尚不清楚PI 3-激酶如何相互作用 因此，使用酸Smase，该提案的具体目的是：1）确定 p85中最小结合结构域与酸相互作用 评估YXXM，NPXY和富含脯氨酸的酸smase的作用 与p85的相互作用。