ACTIVATION OF PROSTATE SPECIFIC ANTIGEN PRECURSOR

前列腺特异性抗原（PSA）是一种前列腺酶， 意义 作为一种蛋白水解酶，它切割精液凝块 蛋白质释放精子受精。 它被牵连到 不育症，因为精液粘稠度高的男性精子异常 运动力和经常不育。 它还可以调节细胞生长 通过切割胰岛素生长因子结合蛋白（IGFBP）， 释放胰岛素生长因子（IGF）进入循环。 有 最近的证据表明，前列腺癌增加了活性水平， 在被α-1-抗胰凝乳蛋白酶灭活之前，它是PSA的形式。 的 前体形式（酶原或pro-PSA），如cDNA所预测的，需要 蛋白水解活化 如果我们能发现前列腺特异性抗原前体是如何被激活的， 可能阐明影响PSA酶水平的特定事件 疾病中的活动。 为了了解亲PSA是如何 由前列腺特异性酶激活，并测试假设， 可以改变该推定激活剂的表达和/或活性 在某些疾病状态下，我们建议： 1.前列腺组织中前列腺特异性抗原激活剂的分离和鉴定 以重组前列腺特异抗原为底物， 2.前列腺特异性抗原前体激活因子的克隆和表达。 3.测试候选激活剂：hGK-1，前列腺特异性丝氨酸 蛋白酶 4.分析不同疾病状态下pro-PSA激活剂的水平 应用免疫

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.