TNFA RECEPTOR CD120A INDUCED SIGNALING IN MACROPHAGES

TNFA 受体 CD120A 在巨噬细胞中诱导信号传导

• 批准号: 2415678
• 负责人: David W. Riches
• 金额: $ 24.01万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2415678
• 关键词: CD antigens; biological signal transduction; cytokine receptors; enzyme activity; gene expression; guanine nucleotide binding protein; macrophage; molecular cloning; phosphoproteins; protein kinase; protein purification; protein structure function; receptor binding; tumor necrosis factor alpha

DESCRIPTION (Adapted from the applicant's abstract and specific aims): Tumor necrosis factor alpha (TNFa) has been implicated in many human disease processes especially those involving the lung as macrophages appear to be important target cells. TNFa is recognized by the cell surface receptors CD120a, (p55) and CD120b (p75). Ligation and aggregation of CD120a (p55) are necessary for the induction of the majority of cellular responses to TNFa including the induction of nitric oxide and insulin-like growth factor-1 expression by macrophages. Several signal transduction mechanisms have been reported to be activated in response to activated TNFa including a kinase cascade that mediates the activation of p42mapk/erk2. It is not known how this kinase cascade is coupled to CD120a (p55). It is hypothesized that signalling through CD120a (p55) is initiated by the phosphoproteins pp95 and/or pp120 which, through their intrinsic association with the intracellular domain of CD120a (p55), enable communication between the receptor and the distal kinase signaling cascade via RAS. The specific aims are: 1) to purify and clone the phosphoproteins, pp95 and pp120, that are constitutively associated with the intracellular domain (ICD) of CD120a (p55); 2) to investigate the functions of pp95 and pp120 and to define the region(s) within the ICD of CD120a (p55) that interact with pp95 and pp120; and 3) to determine the upstream kinase(s) and signalling components responsible for activating p42mapk/erk2.

描述（改编自申请人的抽象和具体目标）： 肿瘤坏死因子 α (TNFa) 与许多人类疾病有关 疾病过程，尤其是涉及肺部巨噬细胞的疾病过程 似乎是重要的靶细胞。 TNFa 被细胞识别 表面受体 CD120a、(p55) 和 CD120b (p75)。 结扎和 CD120a (p55) 的聚集对于诱导 大多数细胞对 TNFa 的反应，包括诱导硝酸 巨噬细胞表达氧化物和胰岛素样生长因子-1。 据报道，多种信号转导机制 响应于活化的 TNFa 而被激活，包括激酶级联反应 介导 p42mapk/erk2 的激活。 尚不清楚这是如何 激酶级联与 CD120a (p55) 偶联。 假设 通过 CD120a (p55) 的信号传导由磷蛋白 pp95 启动 和/或 pp120，通过它们与 CD120a (p55) 的胞内结构域，使细胞之间能够进行通信 受体和通过 RAS 的远端激酶信号级联。 具体的 目标是：1) 纯化和克隆磷蛋白 pp95 和 pp120， 与细胞内结构域 (ICD) 组成型相关 CD120a (p55); 2) 研究pp95和pp120的功能和 定义 CD120a (p55) 的 ICD 内相互作用的区域 与 pp95 和 pp120； 3) 确定上游激酶和 负责激活 p42mapk/erk2 的信号传导组件。