NEW CLASS OF GROWTH FACTORS RELATED TO TGF-B

与 TGF-B 相关的新型生长因子

• 批准号: 2403320
• 负责人: SE-JIN LEE
• 金额: $ 19.95万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-08 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2403320
• 关键词: SDS polyacrylamide gel electrophoresis; cell differentiation; chemical binding; complementary DNA; embryogenesis; gene expression; growth factor receptors; immunochemistry; in situ hybridization; laboratory mouse; mature animal; nucleic acid probes; nucleic acid sequence; oligonucleotides; polymerase chain reaction; protein purification; protein structure function; southern blotting; transforming growth factors; western blottings

The transforming growth factor-beta superfamily of growth and differentiation factors encompasses a group of proteins affecting a wide range of differentiation processes. Because many of these differentiation processes are essential for normal embryonic development, an understanding of the expression and function of these family members would provide insights into how normal regulatory events induced by these factors may go awry to perturb fetal development and how the actions of these factors at ectopic sites or at inappropriate times during adult life may contribute to the generation of a cancer cell. Previous work from this laboratory has identified eight novel mammalian members of this superfamily. Three of these novel factors (GDF-5, GDF-6, and GDF-7) form a new subgroup within the larger superfamily. One of these (GDF-5) appears to be expressed at high levels in adult uterus and in mid-gestation embryos. The overall aim of this proposal is to investigate the roles that this new subfamily plays both during embryonIc development and in adult tissues. The specific aims are to Isolate additional members of this subfamily; to isolate and sequence full-length cDNA clones encoding GDF-5, GDF-6, and GDF-7; to raise antibodies against each of these factors; to determine their patterns of expression in embryos and in adult tissues using immunohistochemical and in situ hybridization methods; to purify GDF-5, GDF-6, and GDF-7 proteins from mammalian cells engineered to overproduce these factors; and to determine the distribution of their receptors. The structural homology between these new factors and the other family members suggests that GDF-5, GDF-6, and GDF-7 may play important roles in mediating developmental decisions related to cell differentiation. The expression of GDF-5 in the uterus suggests that it may be involved either directly or indirectly in regulating early embryogenesis. By analogy with other family members, these new family members have the potential to be used for both diagnostic and therapeutic applications in a variety of clinical settings.

生长和转化生长因子-β超家族 分化因子包含一组影响广泛的蛋白质 分化过程的范围。因为许多这些差异化 过程对于正常胚胎发育至关重要，了解 这些家庭成员的表达和功能的研究将提供 深入了解这些因素引发的正常监管事件可能如何发展 错误地扰乱胎儿发育以及这些因素的作用如何 异位部位或成年后的不适当时间可能会导致 到癌细胞的产生。该实验室之前的工作 确定了该超家族的八种新哺乳动物成员。三个 这些新因子（GDF-5、GDF-6 和 GDF-7）形成了一个新的亚组 更大的超家族。其中之一 (GDF-5) 似乎表达于 在成人子宫和妊娠中期胚胎中含量较高。总体目标 该提案的目的是调查这个新亚科所扮演的角色 在胚胎发育期间和成人组织中。具体目标 隔离该亚科的其他成员；隔离和 对编码 GDF-5、GDF-6 和 GDF-7 的全长 cDNA 克隆进行测序；到 提高针对这些因素的抗体；来确定他们的 使用胚胎和成人组织中的表达模式 免疫组织化学和原位杂交方法；纯化 GDF-5， 来自哺乳动物细胞的 GDF-6 和 GDF-7 蛋白经过改造可过量产生 这些因素；并确定其受体的分布。这 这些新因子与其他家族成员之间的结构同源性 表明 GDF-5、GDF-6 和 GDF-7 可能在 介导与细胞分化相关的发育决策。这 GDF-5 在子宫中的表达表明它可能与 直接或间接调控早期胚胎发生。类推 其他家庭成员，这些新家庭成员有潜力成为 用于各种诊断和治疗应用 临床环境。