TEM5 Ligand Hunt

TEM5 配体搜寻

• 批准号: 6952069
• 负责人: Bradley D St Croix
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6952069
• 关键词: angiogenesis; cell line; cell surface receptors; drug screening /evaluation; gene expression; human tissue; ligands; receptor binding

Tumors are dependent upon new blood vessel formation, or angiogenesis, for expansive growth. Our recent analysis of gene expression in tumor endothelium led to the identification of a G-protein coupled receptor (GPCR) called Tumor endothelial marker 5 (TEM5). In an attempt to understand the role of TEM5 in angiogenesis, we have embarked upon a hunt for its physiological ligand. For this, we have generated stable TEM5 transfectants of 293 cells, and as a screen for ligand activity are taking advantage of the ability of most GPCRs to stimulate the release of calcium into the cytosol upon ligand stimulation. We will attempt to biochemically purify the TEM5 ligand from crude extracts of angiogenic tissues using the calcium mobilization assay as a screen. The cell based calcium assay may also be used to screen drug libraries to find natural or synthetic agonists or antagonitst of TEM5.

肿瘤取决于新的血管形成或血管生成，以进行广泛的生长。我们最近对肿瘤内皮中基因表达的分析导致鉴定出称为肿瘤内皮标记5（TEM5）的G蛋白偶联受体（GPCR）。为了了解TEM5在血管生成中的作用，我们开始寻找其生理配体。为此，我们已经生成了293个细胞的稳定TEM5转染剂，作为配体活性的筛选，我们利用了大多数GPCR在配体刺激时刺激钙释放到细胞质中的能力。我们将尝试使用钙动员分析作为筛选来从生化纯化血管生成组织的TEM5配体。基于细胞的钙测定也可用于筛选药物库，以找到天然或合成的激动剂或TEM5的拮抗作用。