Mesoderm and neuron induction and activin signaling

中胚层和神经元诱导和激活素信号传导

• 批准号: 09044316
• 负责人: SUGINO Hiromu
• 金额: $ 1.54万
• 依托单位: University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09044316/
• 关键词: activin; follistatin; heparan sulfate; apoptosis; development; organizer; endocytosis; オ-ガナイザー; ヘパラン硫酸

Activin belonging to the TGF-beta superfamily binds to and signals through a receptor complex comprising two transmembrane serine/threonine kinases, called type I and type II.So far, two type II (ActR-IIA,-IIB) and two type I (ActRA-IA,IB) activin receptors have been cloned from mammalian sources. In this study, we attempted to elucidate the role of type I receptors in activin signaling for growth, differentiation and apoptosis, and obtained following results.(1) We established stable HS-72 transfectants overexpressing ActR-IA or ActR-IB by the electroporation procedure. Overexpression of ActR-IA suppressed activin-induced cell-cycle arrest in the G1 phase caused by inhibition of retinoblastoma protein phosphorylation through induction of p21, a cyclin-dependent kinase inhibitor, and subsequent apoptosis. In contrast, HS-72 clones that overexpressed ActR-IB significantly facilitated activin induced apoptosis. These results indicate that ActRA-IA and ActR-IB are distinct from each other … More in activin signal transduction.(2) Follistain (activin-binding protein) was found to promote the binding of activin to cell surface heparan sulfate. When the cells were incubated with ^<125>I-activin in the presence of follistatin, significant degradation of activin was observed.This activin degradation was abolished by heparan sulfate, chloroquine, and lysosomal protease inhibitors. These results indicate that cell-associated follistain accelerates the uptake of activin into cells, leading to increased degradation by lysosomal enzymes, and thus plays a role in the activin clearance system.(3) In order to understand the role of follistain-related protein (FRP) in Xenopus embryogenesis, we carried out whole mount in situ hybridization. FRP expression was found to start at stage 10 of Xenopus embryos in the organizer region, suggesting that like follistatin, FRP functions as a organizer factor. The FRP expression in the notochord and floor plate was observed at the neural stage through the tailbud stage, suggesting its role in induction of neural structures. Less

属于TGF-β超家族的激活素与包含两种跨膜丝氨酸/苏氨酸激酶（称为I型和II型）的受体复合物结合并通过其发出信号。迄今为止，已经从哺乳动物来源中克隆了两种II型（ActR-IIA，-IIB）和两种I型（ActRA-IA，IB）激活素受体。在本研究中，我们试图阐明I型受体在激活素信号传导中对生长、分化和凋亡的作用，并获得了以下结果。(1)我们通过电穿孔方法建立了稳定的过表达ActR-IA或ActR-IB的HS-72转染子。ActR-IA的过表达抑制了激活素诱导的细胞周期停滞在G1期，这是由通过诱导p21（一种细胞周期蛋白依赖性激酶抑制剂）抑制视网膜母细胞瘤蛋白磷酸化和随后的凋亡引起的。相反，过表达ActR-IB的HS-72克隆显著促进激活素诱导的细胞凋亡。这些结果表明ActRA-IA和ActR-IB彼此不同 ...更多信息 在激活素信号转导中。(2)发现卵泡抑素（激活素结合蛋白）促进激活素与细胞表面硫酸乙酰肝素的结合。在<125>卵泡抑素存在的情况下，将细胞与^I-激活素一起孵育，观察到激活素的显著降解。硫酸乙酰肝素、氯喹和溶酶体蛋白酶抑制剂可消除这种激活素降解。这些结果表明，细胞相关卵泡抑素加速激活素摄入细胞，导致溶酶体酶降解增加，因此在激活素清除系统中发挥作用。(3)为了了解卵泡抑素相关蛋白（FRP）在非洲爪蟾胚胎发生中的作用，我们进行了整体原位杂交。FRP的表达被发现开始于非洲爪蟾胚胎的第10阶段的组织者区域，这表明像卵泡抑素，FRP作为一个组织者因子的功能。FRP在神经期至尾芽期的脊索和底板中均有表达，提示其在神经结构的诱导中起作用。少

项目成果

Jun′ichi Mashimo: "Decrease in the expression of a novel TGF β1-inducible and ras-recision gene,TSC-36,in human cancer cells" Cancer Letters.113. 213-219 (1997)

Junichi Mashimo：“人类癌细胞中新型 TGF β1 诱导型和 ras 切除基因 TSC-36 的表达减少”Cancer Letters.113-219 (1997)。

Hiromu Sugino: "Follistatin and its role as an activin-binding protein" The Journal of Medical Investigation. 44. 1-14 (1997)

Hiromu Sugino：“卵泡抑素及其作为激活素结合蛋白的作用”《医学调查杂志》。

Osamu Hashimoto: "A novel role of follistatin, an activin-binding protein, in the inhibition of activin action in rat pituitary cells" J.Biol.Chem.272. 13835-13842 (1997)

Osamu Hashimoto：“卵泡抑素（一种激活素结合蛋白）在抑制大鼠垂体细胞激活素作用中的新作用”J.Biol.Chem.272。

Norio Haneji: "Identification of alpha-fodrin as a candidate autoantaigen in primary Sjogren's syndrome" Science. 276. 604-607 (1997)

Norio Haneji：“α-胞质蛋白作为原发性干燥综合征候选自身抗原的鉴定”《科学》。

Norio Haneji: "Identification of α-fodrin as a candidate autoantigen in primary Sjogren′s syndrome" Science. 276. 604-607 (1997)

Norio Haneji：“α-胞质蛋白作为原发性干燥综合征候选自身抗原的鉴定”《科学》276. 604-607 (1997)。