Androgen signaling and kinase regulation in PCA

描述(由申请人提供)：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活级联反应来诱导细胞反应。前者被广泛认可，因为雄激素受体本身就是一种转录因子。后者在最近几年已经开始受到重视，这主要是因为人们意识到磷酸化是几乎所有细胞过程中不可或缺的一部分。然而，这两种机制并不是相互排斥的，因为转录激活可以导致激酶或磷酸酶的上调，从而直接影响磷酸化信号转导。目前的建议涉及一种新的丝氨酸激酶，它被雄激素转录激活，进而调节雄激素受体的活性。与正常的对应物相比，它在前列腺癌细胞中通常过表达。它是雄性细胞的特长，似乎是来自雄激素和生长因子的信号的集成者。 该提案有三个具体目标： 1.确定MAK是雄激素激活的靶点。 1.研究MAK对雄激素受体的调节作用。 1.研究MAK对雄激素前列腺癌生长的调节作用。

DESCRIPTION (provided by applicant): 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.