PURIFICATION OF HUMAN PLATELET-DERIVED GROWTH FACTOR

人血小板衍生生长因子的纯化

• 批准号: 3501414
• 负责人: J FOULKES
• 金额: $ 4.95万
• 依托单位: OSI PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3501414
• 关键词: affinity chromatography; antiatherogenic agent; atherosclerosis; binding proteins; bioassay; cell bank /registry; cell growth regulation; enzyme inhibitors; enzyme mechanism; growth factor receptors; human tissue; immunochemistry; membrane proteins; placenta; platelet derived growth factor; protein tyrosine kinase; radioassay; radiotracer; receptor

The two most prevalent causes of death in Western civilization are myocardial and cerebral infarctions. These conditions are primarily the result of atherosclerotic lesions which occlude the blood vessels supplying the heart and brain. Considerable evidence has now accumulated which suggest that platelet-derived growth factor (PDGF) stimulates the growth of the cells which form these lesions. Localized high concentrations of PDGF are thought to arise at the lesions due to its release from damaged endothelium and adhering platelets at the lesion site. PDGF exerts its mitogenic effect on cells through a specific plasma membrane PDGF receptor protein-tyrosine kinase. The ultimate objective of the proposed project is to find specific inhibitors of PDGF receptor kinase activity for evaluation as therapeutic drugs in the treatment of atherosclerosis. In order to do this, Phase I of the project will purify the human PDGF-receptor and develop an assay for PDGF-dependent, PDGF receptor protein-tyrosine kinase activity, which is capable of being automated so that large numbers of potential inhibitor compounds can be screened. The potential importance of finding a drug which inhibits PDGF action is underlined by the fact that annually in the USA alone about 765,000 people die of heart disease, and 154,000 of cerebrovascular diseases.

西方文明中最普遍的死亡原因是 心肌和脑梗塞。 这些条件是 主要是动脉粥样硬化病变的结果 血管提供心脏和大脑。 大量证据 现在积累了，这表明血小板衍生的生长 因子（PDGF）刺激形成这些细胞的生长 病变。 局部高浓度的PDGF被认为 由于其从受损的内皮释放而出现在病变上 并在病变部位粘附血小板。 PDGF发挥其作用 通过特定的质膜PDGF对细胞的有丝分裂作用 受体蛋白 - 酪氨酸激酶。 最终目标 拟议的项目是找到PDGF受体的特定抑制剂 作为治疗药物评估的激酶活性 治疗动脉粥样硬化。 为了做到这一点， 项目将净化人类PDGF受体并开发一种测定法 对于PDGF依赖性，PDGF受体蛋白 - 酪氨酸激酶活性， 能够自动化，以便大量 可以筛选潜在的抑制剂化合物。 潜力 寻找抑制PDGF作用的药物的重要性是 仅每年在美国就大约765,000，这一事实强调了 人们死于心脏病，154,000个脑血管死亡 疾病。