Androgen signaling and kinase regulation in PCA

PCA 中的雄激素信号传导和激酶调节

• 批准号: 6918172
• 负责人: Hsing-Jien Kung
• 金额: $ 23.56万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6918172
• 关键词: androgen receptor; androgens; athymic mouse; biological signal transduction; clinical research; gene expression; human subject; phosphorylation; prostate neoplasms; protein kinase

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.

描述（由申请人提供）：目前的建议基于以下假设：雄激素通过基因表达和激酶级联反应诱导细胞反应。前者被广泛认可，因为雄激素本身的受体是转录因子。近年来，后者已经开始受到赞赏，这在很大程度上是由于认识到磷酸化是几乎所有细胞过程的组成部分。但是，这两种机制并非互斥，因为转录激活会导致激酶或磷酸酶的上调，从而直接影响磷酸磷酸信号。目前的建议与一种新型的丝氨酸激酶有关，该激酶被雄激素转录激活，进而调节雄激素受体的活性。与正常对应物相比，它在前列腺癌细胞中通常过表达。它是雄性细胞的特殊性，似乎是来自雄激素和生长因子的信号的积分器。 该提案有三个具体目标： 1。将mak描述为雄激活的目标。 1。将mak表征为雄激素受体的调节剂。 1。将mak作为雄激素前列腺癌生长的调节剂。