权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Signal Transduction Mechanism in differentiation and Development of Follicular Granulosa Cells.

滤泡颗粒细胞分化和发育的信号转导机制。

基本信息

批准号：
02454541
负责人：
SUGINO Hiromu
金额：
$ 4.35万
依托单位：
The Institute of Physical and Chemical Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

Activin was originally isolated from mammalian ganads as a stimulator for FSH secretion by pituitary cells. the primary structures was found to be very similar to TGF-beta. Recent studies have verified that, like TGF-beta, mfivin has vadous fimctions in various biological reactions including development, differentiation and morphogenesis. In this project, we focused on elucidation of the mechanism for activin signal msduction.(1)We found in rat ovaly and bovine pituitary an activin-binding protein with a specific and high affinity for activin, and proved that it was identical to follistatin, which was initially obtained from pig ovary as an FSHsecretion suppressor. We also demonstrated that follistatin exerts a neutralizing effect on activin activity in various systems. These inhibitory effects of follistatin on activin actions can be explained by our finding that folhstatin binds directly to activin to form an inactive complex. Follistatin very likely plays a significant role in the regulation of various actions of activin. (2)Follistatin secreted by cultured rat granulosa cells was shown to associate with cell surface by affinity labeling with ^<125>I-activin. It bound to the heparan sulfate side chains of proteoglycans on the cell surface. Cell-bound follistatin may capture activin in the matrix and at the cell surface and regurate the various actions of activin. (3)An activin receptor protein was isolated by affinity chromatography on an activin-immobilizedcolumn from membrane fractions of several cell cultures including mouse Friend leukemia cell F5-5, human erythroleukemia cell K562 and mouse EC cell P19. SDS-PAGE of the prepretion showed one band of 70 kDa. The amino acid sequence of the first 18 residues revealed that the purified receptor is a member of the activin receptor family.

激活素最初是从哺乳动物生殖器中分离出来的，作为垂体细胞促卵泡刺激素分泌的刺激物。初级结构被发现与tgf -非常相似。最近的研究证实，mfivin与tgf - β一样，在包括发育、分化和形态发生在内的各种生物反应中具有多种功能。在本项目中，我们重点阐明了激活素信号的诱导机制。(1)我们在大鼠卵巢和牛垂体中发现了一种对激活素具有特异性和高亲和力的激活素结合蛋白，并证明其与最初从猪卵巢中获得的卵泡抑素相同。我们还证明了卵泡抑素在各种系统中对激活素的活性有中和作用。卵泡抑素对激活素的抑制作用可以通过我们的发现来解释，即卵泡抑素直接与激活素结合形成无活性复合物。Follistatin很可能在调节激活素的各种作用中起着重要作用。(2)培养的大鼠颗粒细胞分泌的Follistatin通过与^<125>I-activin的亲和标记显示与细胞表面相关。它结合到细胞表面的硫酸肝素蛋白聚糖侧链上。细胞结合的卵泡抑素可以在基质和细胞表面捕获激活素，并调节激活素的各种作用。(3)用亲和层析法从小鼠Friend白血病细胞F5-5、人红白血病细胞K562和小鼠EC细胞P19的膜层中分离到激活素受体蛋白。预制品SDS-PAGE显示一条70 kDa的条带。前18个残基的氨基酸序列表明纯化的受体是激活素受体家族的成员。