CALCIUM RECEPTORS AND PROLIFERATIVE SIGNALS

描述：拟议项目的目标是建立的作用， 钙敏感受体（CaR）在调节细胞增殖中的作用 成纤维细胞，并确定信号转导途径相互作用， 车 为了实现这一目标，Rodland博士的研究计划有四个具体的目标。 目的：1）确定是否需要细胞内钙的释放 对于来自CaR的下游信号传导（例如c-Src的激活， 最终激活ERK激酶）; 2）确定Src是否 激活、Shc磷酸化和p62 dok与RasGAP的结合是 3）为了确定Ras是否是ERK 1的CaR依赖性激活所必需的; 需要激活和刺激Ras-Raf-Me级联反应， CaR依赖的ERK 1激活; 4）为了确定哪些响应于 细胞外钙依赖于CaR的表达，使用CaR null 从基因敲除小鼠产生的成纤维细胞。 这些目标将会实现 通过使用特异性抑制剂和显性负突变体的实验， 假设的信号通路中的关键参与者

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