FUNCTIONAL CHARACTERIZATION OF TRANSFORMING GROWTH FACTORS AND THEIR RECEPTORS

转化生长因子及其受体的功能特征

• 批准号: 4692426
• 负责人: L M WAKEFIELD
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4692426
• 关键词: Retroviridae; antibody formation; cell growth regulation; immunogenetics; membrane activity; monoclonal antibody; oncogenes; oncogenic virus; radioimmunoassay; tissue /cell culture; transforming growth factors; viral carcinogenesis

Transforming growth factors (TGFs) are acid-stable polypeptides that induce a reversible phenotypic transformation of normal indicator cells such that they will grow in an anchorage-independent manner in soft agar, a property characteristic of transformed cells. The purpose of this project is to determine the role that endogenously-produced TGFs may play in the growth of normal and transformed cells and to characterize their mode of action at a biochemical level. To this end, polyclonal antisera have been raised to the TGFs, and development of monoclonal antibodies is in progress. The effects of these antibodies on the anchorage-dependent and -independent growth of normal and transformed cells are being investigated and will be analyzed in terms of the biochemical functions affected. Since the first step in the interaction of TGFs with the cell is binding of the growth factor to the cell surface, initial investigations have concentrated on the characterization of cell surface receptors for TGFs. Development of radioreceptor assay for TGF-beta, a TGF that depends on a second TGF (EGF or TGF-alpha) for activity, has allowed identification of a specific high affinity receptor for TGF-beta on all normal and transformed cell lines studied so far. The receptor appears to be a disulphide-linked dimer that does not undergo ligand-induced autophosphorylation or clustering. Receptor properties are modulated by transformation but binding of TGF-beta to its receptor does not appear to be a major control point in TGF-beta action. Human cell lines and tissues are being screened for an abundant source of the receptor for use as a starting material for receptor purification and as an immunogen for the production of anti-receptor monoclonal antibodies. Further characterization of the role of endogenously-produced TGFs and their interaction with the cell surface receptor should help elucidate the role these molecules may play in the process of carcinogenesis.

转化生长因子(TGFs)是一种酸性稳定的多肽，可诱导 正常指示细胞的可逆表型转化 它们将在软琼脂中以独立于锚地的方式生长，软琼脂是一种 转化细胞的特征。这个项目的目的是 确定内源产生的转化生长因子在生长中可能发挥的作用 正常和转化的细胞，并描述它们在 一个生化水平。为此，多克隆抗血清已被提高到 目前正在研制抗肿瘤生长因子和单抗的研究。这个 这些抗体对锚定依赖和非锚定依赖的影响 正在研究正常细胞和转化细胞的生长情况，并将 从影响生化功能的角度进行分析。从第一次 转化生长因子与细胞相互作用的步骤是结合生长 因素对细胞表面的影响，最初的研究集中在 转化生长因子细胞表面受体的特性。发展中的 放射受体法检测依赖于第二种转化生长因子(EGF)的转化生长因子-β 或转化生长因子-α)的活性，已允许识别特定的高 所有正常和转化细胞系上的转化生长因子-β亲和力受体 目前为止已经研究过了。该受体似乎是一种二硫键连接的二聚体 不经历配体诱导的自磷酸化或聚集。 受体特性受转化生长因子-β的转化和结合的调节 与其受体的结合似乎不是转化生长因子-β的主要控制点 行动。正在对人类细胞系和组织进行筛选，以寻找丰富的 受体的来源，用作受体的起始材料 抗受体蛋白的纯化及其作为免疫原生产的研究 单克隆抗体。角色的进一步表征 内源性转化生长因子及其与细胞表面的相互作用 受体应该有助于阐明这些分子可能在 致癌过程。