Restin: mutants, receptor cloning and signaling studies.

Restin：突变体、受体克隆和信号传导研究。

• 批准号: 6465311
• 负责人: Ramani Ramchandran
• 金额: $ 15.97万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-03 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6465311
• 关键词: Address; Angiogenesis Inhibitors; Antineoplastic Agents; Binding; Biochemical; C-terminal; Cell surface; Clone Cells; Cloning; Collagen; Drug resistance; Endothelial Cells; Event; Human; Mediating; Molecular Biology; Proteins; Signal Transduction; Structure-Activity Relationship; Techniques; Toxic effect; cancer therapy; chemotherapy; mutant; receptor; restin; tumor; Address; Angiogenesis Inhibitors; Antineoplastic Agents; Binding; Biochemical; C-terminal; Cell surface; Clone Cells; Cloning; Collagen; Drug resistance; Endothelial Cells; Event; Human; Mediating; Molecular Biology; Proteins; Signal Transduction; Structure-Activity Relationship; Techniques; Toxic effect; cancer therapy; chemotherapy; mutant; receptor; restin; tumor

Anti-angiogenic molecules have tremendous potential in the treatment of cancer. Anti-angiogenic therapy has several benefits over conventional chemotherapy as different tumors can be treated with less toxicity. Most significantly, drug resistance is unlikely. Despite these potential advantages, the utility of current anti-angiogenic agents is limited since the mechanism of action of these proteins is unknown. The PI?s long term objective is to study the mechanism of action of antiangiogenic proteins and to identify the cell surface molecules that interact with these proteins. This proposal focuses on Restin, a C-terminal fragment of the NC1 domain in human collagen XV. This fragment possesses antimigratory function against endothelial cells. This proposal plans to understand the mechanism of action of restin with the following specific aims: Specific Aim 1: To define the structure-function relationship of restin. Specific Aim 2: To determine the intracellular signaling events mediated by restin. Specific Aim 3: To identify and clone the cell surface binding partner(s) receptor for restin. We will use molecular biology and biochemical techniques to address these aims. Once the mechanism of restin?s action has been elucidated, we will understand better the utility of restin and similar agents as anti-cancer drugs.

抗血管生成分子在癌症治疗中具有巨大的潜力。抗血管生成疗法已有 与常规化疗相比，由于毒性较小的毒性可以治疗不同的肿瘤。最重要的是，耐药性不太可能。尽管有这些潜在的优势，但由于这些蛋白质的作用机理尚不清楚，目前的抗血管生成剂的实用性受到限制。 PI的长期目标是研究抗血管生成蛋白的作用机理，并鉴定与这些蛋白质相互作用的细胞表面分子。该提议着重于人类胶原蛋白XV中NC1结构域的C末端片段。该碎片具有针对内皮细胞的抗移民功能。该提案计划以以下具体目的了解Restin的作用机理： 特定目的1：定义Restin的结构功能关系。 特定目的2：确定restin介导的细胞内信号传导事件。 特定目的3：识别和克隆restin的细胞表面结合伴侣的受体。 我们将使用分子生物学和生化技术来解决这些目标。一旦阐明了Restin作用的机制，我们将更好地理解restin和类似药物的效用，就像抗癌药物一样。