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E63-1 AND STEROID/CALCIUM-REGULATED CROSSTALK

E63-1 和类固醇/钙调节串扰

基本信息

批准号：
6180897
负责人：
ANDREW J ANDRES
金额：
$ 15.84万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-09-15 至 2001-08-31
项目状态：
已结题

项目摘要

Steroid hormones are small regulatory molecules that profoundly influence basic processes of growth and homeostasis in developing organisms. Presumably, this occurs when the hormone induces a qualitative change in the pattern of gene expression. Thus, identifying and characterizing the gene targets for steroid action, and how they are translated into biological changes in the target tissue, is a primary goal of this research. Specifically, this proposal is a logical extension of the unexpected discovery made during the PI's post-doctoral studies on tissue-specific (salivary gland) steroid-regulated genes in the fruit fly Drosophila melanogaster. Briefly, it was shown that E63-1, a primary (early) target for the Drosophila steroid ecdysone, encodes a high-affinity Ca2+-binding protein. This discovery was novel and exciting because most of the previously characterized early targets were shown to encode transcription factors. This finding provides the first link between steroid-regulated and Ca2+-regulated signaling pathways in Drosophila. Thus, one is afforded a unique opportunity to investigate this possible "crosstalk" in a genetically tractable organism in the context of an already well characterized molecular hierarchy. The overall hypothesis being addressed is that E63-1 functions to coordinate a steroid- and calcium-mediated regulatory pathway in the salivary gland. The goals are to dissect this pathway at the molecular level, investigate the possibility that E64-1 encodes a signal transduction molecule, and apply this information to other systems. The specific aims are as follows: 1) Genetically manipulate the levels of E63-1 protein and investigate these effects on the physiological state of the tissue (secretory activity, gene expression manifested as puffs, intracellular Ca2+ changes). 2) Further define the mechanism by initiating a molecular screen for downstream acceptor proteins of E63-1.

类固醇激素是一种小的调节分子，影响发育中的基本生长和体内平衡过程有机体据推测，这发生在激素诱导基因表达模式的质的变化。因此，在本发明中，鉴定和表征类固醇作用的基因靶标，以及它们如何转化为目标的生物变化组织，是这项研究的主要目标。具体而言，这项提案这是一个合乎逻辑的延伸，意外的发现， PI的组织特异性（唾液腺）博士后研究果蝇中的类固醇调节基因。简而言之，显示E63-1，一个主要的（早期）靶点，果蝇类固醇蜕皮激素，编码高亲和力的Ca 2+结合蛋白蛋白这一发现是新奇和令人兴奋的，因为大多数的先前表征的早期靶标显示编码转录因子这一发现提供了第一个联系，类固醇调节和Ca 2+调节的信号通路果蝇因此，人们获得了一个独特的机会，研究这种可能的“串扰”，在一个遗传上易于处理的在已经很好表征的分子背景下，等级制度。提出的总体假设是，E63-1的功能是协调类固醇和钙介导的调节途径，唾液腺我们的目标是解剖这条途径，在分子水平上，研究E64-1编码一种信号转导分子，并将此信息应用于其他系统. 具体目标如下： 1)基因操纵E63-1蛋白水平，研究这些对组织生理状态的影响（分泌活性，基因表达表现为泡沫，细胞内Ca 2+变化）。 2)通过启动分子筛选进一步确定机制 E63-1的下游受体蛋白。