ACTIVATION OF PROSTATE SPECIFIC ANTIGEN PRECURSOR

前列腺特异性抗原前体的激活

• 批准号: 6175995
• 负责人: THOMAS K TAKAYAMA
• 金额: $ 11.53万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-15 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6175995
• 关键词: Escherichia coli; SDS polyacrylamide gel electrophoresis; affinity chromatography; bacterial proteins; enzyme activity; enzyme induction /repression; enzyme linked immunosorbent assay; fertility; gel filtration chromatography; high performance liquid chromatography; human tissue; immunocytochemistry; ion exchange chromatography; male; molecular cloning; monoclonal antibody; prostate disorder; prostate specific antigen; protease inhibitor; serine proteinases; tissue /cell culture; zymogens

Prostate specific antigen (PSA) is a prostatic enzyme with biological significance. As a proteolytic enzyme, it cleaves seminal coagulum proteins to release sperm for fertilization. It has been implicated in infertility because men with highly viscous semen have abnormal sperm motility and are often infertile. It may also regulate cellular growth by cleaving insulin growth factor-binding proteins (IGFBP's), thereby releasing insulin growth factor (IGF) into the circulation. There is recent evidence that prostate cancer increases the level of the active form of PSA before it is inactivated by alpha-1-antichymotrypsin. The precursor form (zymogen or pro-PSA) as predicted by the cDNA requires proteolytic activation. If we can discover how pro-PSA is activated, we may elucidate the specific events affecting the level of PSA enzyme activity in disease stated. In order to understand how the pro-PSA is activated by a prostate-specific enzyme, and to test the hypothesis that the expression and/or activity of this putative activator may be altered in certain disease states, we propose to: 1. Isolate and characterize the activator of pro-PSA from prostate tissue by utilizing recombinant pro-PSA as the substrate. 2. Clone and express the pro-PSA activator. 3. Test a candidate activator: hGK-1, a prostate-specific serine protease. 4. Analyze the level of the pro-PSA activator in various disease states by immunohistochemistry.

前列腺特异性抗原（PSA）是一种具有生物活性的前列腺酶。 意义。 作为一种蛋白水解酶，它可以裂解精浆 释放精子进行受精的蛋白质。 已经被牵连到 由于精液粘稠度高的男性精子异常而导致不育 活动能力差且常常不育。 它还可以调节细胞生长 通过裂解胰岛素生长因子结合蛋白（IGFBP），从而 将胰岛素生长因子（IGF）释放到循环中。 有 最近的证据表明前列腺癌会增加活性物质的水平 在被 α-1-抗胰凝乳蛋白酶灭活之前以 PSA 形式存在。 这 cDNA 预测的前体形式（酶原或 pro-PSA）需要 蛋白水解激活。 如果我们能够发现 pro-PSA 是如何被激活的，我们 可以阐明影响 PSA 酶水平的具体事件 所指出的疾病活动。 为了了解 pro-PSA 是如何 由前列腺特异性酶激活，并检验以下假设： 该推定激活剂的表达和/或活性可能会改变 在某些疾病状态下，我们建议： 1. 从前列腺组织中分离并表征 pro-PSA 的激活剂 利用重组pro-PSA作为底物。 2. 克隆并表达pro-PSA激活剂。 3. 测试候选激活剂：hGK-1，一种前列腺特异性丝氨酸 蛋白酶。 4.分析各种疾病状态下pro-PSA激活剂的水平 通过免疫组织化学。