Androgen signaling and kinase regulation in PCA

描述（由申请人提供）：本提案基于雄激素通过激活基因表达和激酶级联诱导细胞反应的假设。前者被广泛认可，因为雄激素受体本身是一种转录因子。近年来，后者开始受到重视，这主要是因为人们认识到磷酸化是几乎所有细胞过程的组成部分。然而，这两种机制并不相互排斥，因为转录激活可导致激酶或磷酸酶的上调，从而直接影响磷酸化信号传导。本发明涉及一种新的丝氨酸激酶，其被雄激素转录激活并进而调节雄激素受体活性。与正常对应物相比，它通常在前列腺癌细胞中过表达。它是雄性细胞特异性的，似乎是来自雄激素和生长因子的信号的整合者。 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。

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.