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Membrane receptor for 1 alpha, 25(OH)2 - vitamin D3

1 α, 25(OH)2 - 维生素 D3 的膜受体

基本信息

批准号：
6922794
负责人：
CHRISTOPHER J OLIVERA
金额：
$ 0.83万
依托单位：
UNIVERSITY OF CALIFORNIA RIVERSIDE
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-08-01 至 2006-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Vitamin D is a prohormone for the daughter metabolite 1 alpha,,25(OH)2D3, which is a steroid hormone. As a consequence of being highly conformationally flexible, la,25(OH)2D3 presents a wide variety of shapes to its cellular environment. This in turn allows the generation of a variety of biological responses by activation of signal transduction pathways via one or more receptors involved in the production of either classic genotropic transcription of genes and/or rapid non-geriotropic biological responses. The 1 alpha,25(OH)2D3-mediated transcription of genes has been well studied and it is known to regulate a variety of cells and tissues. Conversely, the non-genotropic responses being activated by 1alpha,25(OH)2D3 appear to be mediated by a different signal pathway since the time frame of these responses which occur from seconds to minutes contrary to the genotropic frame of hours. Additionally, these types of responses can be separated from each other using a variety of path or action-specific derived analogs for 1 alpha,25(OH)2D3. The relevance to this proposal occurs in the study of the latter mechanism, in which a putative membrane receptor is believed to be responsible for mediating these responses. Thus, I propose to isolate and biochemical characterize the protein(s) responsible of 1 a,25(OH)2D3-mediated nongenotropic responses in plasma membrane invaginations or vesicles called caveolae. In other systems, caveolae have been linked to other steroid mediated rapid responses in which receptors to the respective ligands were shown to reside. We aim to isolate and purify the proposed membrane receptor which selectively binds 1 a,25(OH)2D3 with high affinity. This followed by characterization of the protein, leading to cloning and expression to learn its biological properties.

描述（由申请方提供）：维生素D是子代谢物1 α，25（OH）2D 3的激素原，是一种类固醇激素。作为高度构象柔性的结果，la，25（OH）2D 3在其细胞环境中呈现出各种各样的形状。这又允许通过经由一种或多种受体激活信号转导途径来产生各种生物应答，所述受体参与基因的经典遗传向性转录和/或快速非老年向性生物应答的产生。1 α，25（OH）2D 3介导的基因转录已被充分研究，并且已知其调节多种细胞和组织。相反，1 α，25（OH）2D 3激活的非遗传性反应似乎是由不同的信号途径介导的，因为这些反应的时间范围从秒到分钟，而遗传性反应的时间范围是小时。此外，这些类型的反应可以使用1 α，25（OH）2D 3的多种途径或作用特异性衍生类似物彼此分离。这一建议的相关性发生在后一种机制的研究中，其中一个假定的膜受体被认为是负责介导这些反应。因此，我建议分离和生化特性的蛋白质（S）负责1 α，25（OH）2D 3介导的非基因型反应质膜内陷或囊泡称为小窝。在其他系统中，小窝已经与其他类固醇介导的快速反应相关联，其中显示存在相应配体的受体。我们的目的是分离和纯化建议的膜受体，选择性结合1 α，25（OH）2D 3具有高亲和力。随后是蛋白质的表征，导致克隆和表达以了解其生物学特性。