ACTIVATION OF PROSTATE SPECIFIC ANTIGEN PRECURSOR

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，它能分解精液凝固物。 释放精子以供受精的蛋白质。它已被牵连到 不育是因为精液高度粘稠的男性精子异常 而且往往是不育的。它还可能调节细胞生长。 通过切割胰岛素生长因子结合蛋白(IGFBP)，从而 向循环中释放胰岛素生长因子(IGF)。的确有 最近的证据表明，前列腺癌增加了活跃分子的水平 PSA在被α-1-抗糜蛋白酶灭活之前的形式。这个 C DNA预测的前体形式(酶原或原PSA)需要 蛋白水解性激活。如果我们能发现前PSA是如何被激活的，我们 可能阐明影响PSA酶水平的具体事件 疾病的活跃性陈述。为了了解支持PSA的人 被一种前列腺特异性酶激活，并检验这一假设 该假定激活剂的表达和/或活性可以改变 在某些疾病状态下，我们建议： 1.前列腺组织中PSA原激活物的分离和鉴定 以重组前PSA为底物。 2.克隆并表达PSA原激活子。 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.分析不同疾病状态下PSA原激活物的水平 采用免疫组织化学方法。

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.