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

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的治疗中具有巨大的潜力。抗血管生成治疗已经 与传统化疗相比有几个好处，因为不同的肿瘤可以以较低的毒性进行治疗。最重要的是，抗药性不太可能。尽管有这些潜在的优势，但由于这些蛋白质的作用机制尚不清楚，目前抗血管生成药物的应用受到限制。S的长期目标是研究抗血管生成蛋白的作用机制，并确定与这些蛋白相互作用的细胞表面分子。本研究的重点是Restin，它是人胶原XV中Nc1结构域的一个C-末端片段。该片段具有抗内皮细胞迁移的功能。该提案计划了解RESIN的行动机制，具体目标如下： 具体目标1：明确restin的结构-功能关系。 特定目的2：确定restin介导的细胞内信号事件。 具体目的3：鉴定并克隆细胞表面结合伙伴(S)的restin受体。 我们将使用分子生物学和生化技术来解决这些目标。一旦瑞斯汀、S的作用机制被阐明，我们就会更好地了解瑞斯汀及其类似药物作为抗癌药物的作用。