HUMAN ERYTHROID-POTENTIATING ACTIVITY

人红细胞增强活性

• 批准号: 3087366
• 负责人: Belinda Rene Avalos
• 金额: $ 7.33万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-08-01 至 1991-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3087366
• 关键词: affinity chromatography; antibody receptor; binding proteins; complementary DNA; erythroid stem cell; erythropoiesis; gene expression; genetic library; genetic manipulation; genetic transcription; hematopoietic growth factor; hormone receptor; human tissue; laboratory rabbit; messenger RNA; molecular cloning; monoclonal antibody; myelogenous leukemia; myeloproliferative neoplasm; neoplastic cell; protein sequence; radioimmunoassay; tissue /cell culture

Hematopoiesis is tightly regulated by a series of hormonal factors that stimulate the proliferation and differentiation of progenitor cells, as well as modulate the functional activity of mature effector cells. Human erythroid-potentiating activity (EPA) is a recently purified and molecularly cloned growth factor which stimulates the growth of erythroid precursors. The precise physiological role of EPA in the regulation of hematopoiesis is unknown. The proposed studies are designed to investigate the mechanisms of action of EPA on normal and neoplastic cells through characterization at the molecular level of the interaction of EPA with its receptor protein. Target cells bearing receptors for EPA as determined by binding of labeled 125I-EPA will be used as a source for purifying the EPA receptor and generating receptor antisera. Molecular clones encoding the EPA receptor will be obtained and used to determine the structure and sequence of the receptor protein and to examine its genomic organization in DNA. The cDNA clones will then be used to study the regulation and expression of the EPA receptor in normal and neoplastic cells. I propose to comprehensively analyze the EPA receptor on normal human peripheral blood and bone marrow cells, various human cell lines, and fresh neoplastic cells. Receptor numbers, binding affinity, and molecular properties of the receptor protein will be studied. Thus, significant differences may be seen in the quantitative or qualitative characteristics of the EPA receptor protein in normal and neoplastic cells which are important in the maintenance of the normal and transformed malignant state. Of particular interest is the possibility of tumor promoting activities or translocations or amplifications of the EPA receptor gene in specific neoplasias, in view of the association of some receptor proteins with oncogenes. Overall, these studies should yield new and important information on the in vivo regulation by EPA of hematopoiesis and its role in the pathophysiology of various disease states. Information gained from these studies should contribute to our basic understanding of the interactions of hematopoietic growth factors and their target cells. On a larger scale, this information should expand our current fundamental knowledge of hematopoietic cell growth and the interaction of growth factors and their receptors in normal and malignant states.

造血受到一系列激素因素的严格调节， 刺激祖细胞的增殖和分化， 以及调节成熟效应细胞的功能活性。 人类 红细胞增强活性 (EPA) 是一种最近纯化和 刺激红细胞生长的分子克隆生长因子 前体。 EPA 在调节中的精确生理作用 造血作用未知。 拟议的研究旨在调查作用机制 通过表征 EPA 对正常细胞和肿瘤细胞的作用 EPA与其受体蛋白相互作用的分子水平。 带有 EPA 受体的靶细胞通过标记的结合来确定 125I-EPA将用作纯化EPA受体的来源和 产生受体抗血清。 编码EPA受体的分子克隆 将获得并用于确定结构和序列 受体蛋白并检查其在 DNA 中的基因组组织。 cDNA 然后克隆将用于研究 EPA 的调控和表达 正常细胞和肿瘤细胞中的受体。 我建议全面分析正常人体的EPA受体 外周血和骨髓细胞、各种人类细胞系和新鲜 肿瘤细胞。 受体数量、结合亲和力和分子 将研究受体蛋白的特性。 因此，显着 差异可能体现在数量或质量特征上 正常细胞和肿瘤细胞中的 EPA 受体蛋白 对于维持正常和转化的恶性细胞很重要 状态。 特别令人感兴趣的是促进肿瘤生长的可能性 EPA受体基因的活性或易位或扩增 鉴于某些受体蛋白的关联，特定肿瘤 与癌基因。 总体而言，这些研究应该会产生有关内部的新的重要信息。 EPA对造血的体内调节及其在病理生理学中的作用 各种疾病状态。 从这些研究中获得的信息应该 有助于我们对造血相互作用的基本理解 生长因子及其靶细胞。 从更大的范围来看，这些信息 应该扩展我们目前对造血细胞的基础知识 正常情况下的生长以及生长因子及其受体的相互作用 和恶性状态。