Androgen signaling and kinase regulation in PCA

目前的建议是基于这样的假设，即雄激素通过激活 基因表达和激酶级联反应。前者被广泛认可，因为受体 雄激素本身是转录因子。后者近年来开始升值，很大程度上是由于 磷酸化是几乎所有细胞过程的组成部分。这两 然而，这些机制并不相互排斥，因为转录激活可导致转录因子的上调。 激酶或磷酸酶，从而直接影响磷酸化信号传导。现时的建议 与一种新的丝氨酸激酶有关，这种激酶被雄激素转录激活， 调节雄激素受体活性。它通常在前列腺癌细胞中过表达，相比之下， 正常的对应。它是雄性细胞特有的，似乎是来自雄激素的信号的整合者 和生长因子。 该提案有三个具体目标： 1.描述MAK作为雄激素激活靶点的特征。 1.探讨MAK作为雄激素受体调节剂的作用。 1.描述MAK作为雄激素前列腺癌生长调节剂的特征。

The present proposal is based on the hypothesis that androgen induces cellular responses via the activation of both gene expression and kinase cascade. The former is widely recognized, since the receptor for androgen itself is a transcriptional factor. The latter has begun to be appreciated in recent years, largely due to the realization that phosphorylation is an integral part for virtually all cellular processes. These two mechanisms however are not mutually exclusive, as transcriptional activation can lead to upregulation of kinases or phosphatases, thereby directly influencing the phosphorylatiion signaling. The present proposal is concerned with a novel serine kinase that is transcriptionally activated by androgen and that in turn regulates androgen receptor activity. It is generally overexpressed in prostate cancer cells, compared to normal counterpart. It is male-cell speciic and appears to be an integrator of signals coming from androgen and growth factor. There are three specific aims of the proposal: 1. To characterize MAK as a target of androgen activation. 1. To characterize MAK as a regulator of androgen receptor. 1. To characterize MAK as a modulator of androgen prostate cancer growth.