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

Intracellular and extracellular control of activin signaling by novel regulatory molecules

新型调节分子对激活素信号传导的细胞内和细胞外控制

基本信息

批准号：
15370058
负责人：
SUGINO Hiromu
金额：
$ 9.79万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

Activins, members of the transforming growth factor (TGF-β) family have various effects on diverse biologic systems, such as erythroid differentiation, bone growth, mesoderm induction, etc.Activin type II receptors (ActRIIs) are the primary receptors that transmit the activin signal to intracellular signaling pathways. Binding of activins to ActRIIs recruits the activin type I receptor and initiates downstream signaling. We have found that PDZ proteins, named activin receptor-interacting proteins (ARIPs), specifically associate with ActRIIs. We have studied the mechanism that ARIPs regulate cell surface expression and cellular localization of ActRIIs. ARIP2 interacts with both ActRIIs and RalBP1 (Ral binding protein 1) through different domains to dramatically change the localization of ActRIIs. Overexpression of ARIP2 enhances endocytosis of ActRIIs. These data indicate that ARIP2 is a novel factor regulating cell surface ActRII expression and activin function.A novel activin binding protein, follistatin-related gene (FLRG) was identified. FLRG protein binds activin and myostatin with a high affinity. The biological activity of FLRG is similar to those of follistatin, however, the regulation and expression patterns of follistatin and FLRG differ. Immunohistochemical analysis shows that FLRG is distributed in spermatogenic cells of the testis, renal tubules, epithelial cells of the lung, and myocardium. Thus, although structurally and functionally similar, follistatin and FLRG likely play distinct roles as activin/GDF binding proteins in vivo.

激活素是转化生长因子 (TGF-β) 家族的成员，对不同的生物系统具有多种作用，如红细胞分化、骨生长、中胚层诱导等。激活素 II 型受体 (ActRII) 是将激活素信号传递到细胞内信号通路的主要受体。激活素与 ActRII 的结合会募集激活素 I 型受体并启动下游信号传导。我们发现 PDZ 蛋白（称为激活素受体相互作用蛋白 (ARIP)）与 ActRII 特异性相关。我们研究了ARIPs调节ActRII细胞表面表达和细胞定位的机制。 ARIP2 通过不同的结构域与 ActRII 和 RalBP1（Ral 结合蛋白 1）相互作用，显着改变 ActRII 的定位。 ARIP2 的过度表达增强 ActRII 的内吞作用。这些数据表明ARIP2是调节细胞表面ActRII表达和激活素功能的新因子。鉴定了一种新的激活素结合蛋白——卵泡抑素相关基因(FLRG)。 FLRG 蛋白以高亲和力结合激活素和肌生长抑制素。 FLRG的生物学活性与卵泡抑素相似，然而，卵泡抑素和FLRG的调控和表达模式不同。免疫组织化学分析显示，FLRG分布于睾丸生精细胞、肾小管、肺上皮细胞和心肌中。因此，虽然结构和功能相似，但卵泡抑素和 FLRG 可能在体内作为激活素/GDF 结合蛋白发挥不同的作用。