Restin: mutants, receptor cloning and signaling studies.

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 与传统化疗相比，它有几个好处，因为不同的肿瘤可以以较低的毒性进行治疗。最重要的是，不太可能出现耐药性。尽管有这些潜在的优势，但目前的抗血管生成剂的效用是有限的，因为这些蛋白质的作用机制是未知的。私家侦探？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。该提案的重点是Restin，人胶原XV中NC 1结构域的C-末端片段。该片段对内皮细胞具有抗迁移功能。该提案计划了解restin的作用机制，具体目标如下： 具体目标1：明确restin的结构与功能关系。 具体目标2：确定由restin介导的细胞内信号传导事件。 具体目标3：鉴定和克隆restin的细胞表面结合伴侣受体。 我们将使用分子生物学和生物化学技术来实现这些目标。一旦休息的机制？的作用已经阐明，我们将更好地了解restin和类似药物作为抗癌药物的效用。

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.