CALCIUM RECEPTORS AND PROLIFERATIVE SIGNALS

钙受体和增殖信号

• 批准号: 6554331
• 负责人: Karin D Rodland
• 金额: $ 19.14万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-07 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6554331
• 关键词: biological signal transduction; calcium flux; cell growth regulation; cell line; cell proliferation; embryo /fetus cell /tissue; enzyme induction /repression; extracellular; fibroblasts; gene induction /repression; gene targeting; genetically modified animals; laboratory mouse; laboratory rat; mitogen activated protein kinase; mutant; receptor expression

DESCRIPTION: The goal of the proposed project is to establish the role of the calcium-sensing receptor (CaR) in regulating the proliferation of fibroblasts, and to define the signal transduction pathways interacting with the CaR. To accomplish this, Dr. Rodland's research plan has four specific aims: 1) To determine whether release of intracellular calcium is required for downstream signaling from the CaR (e.g. activation of c-Src and, ultimately, activation o ERK kinase); 2) To determine whether Src activation, Shc phosphorylation, and p62dok association with RasGAP are required for CaR-dependent activation of ERK1; 3) To determine whether Ras activation and stimulation of the Ras-Raf-Me cascade are required for CaR-dependent activation of ERK1; 4) To determine which responses to extracellular calcium are dependent on expression of the CaR, using CaR null fibroblasts generated from knock-out mice. These aims will be accomplished through experiments using specific inhibitors and dominant negative mutants of the key participants in the hypothesized signaling pathway

描述：拟议项目的目标是确立以下角色： 钙敏感受体（CaR）在调节细胞增殖中的作用 成纤维细胞，并定义与成纤维细胞相互作用的信号转导途径 的CaR。 为了实现这一目标，罗德兰博士的研究计划有四个具体内容 目的： 1) 确定是否需要释放细胞内钙 用于来自 CaR 的下游信号传导（例如 c-Src 的激活和， 最终，激活 ERK 激酶）； 2）判断Src是否 激活、Shc 磷酸化以及 p62dok 与 RasGAP 的关联 ERK1 的 CaR 依赖性激活所需； 3）判断是否Ras Ras-Raf-Me 级联的激活和刺激是 ERK1 的 CaR 依赖性激活； 4) 确定哪些响应 细胞外钙依赖于 CaR 的表达，使用 CaR null 由基因敲除小鼠产生的成纤维细胞。 这些目标将会实现 通过使用特定抑制剂和显性失活突变体的实验 假设的信号通路的关键参与者