Mesoderm and neuron induction and activin signaling

激活素属于转化生长因子-β超家族，通过一个由两个跨膜型丝氨酸/苏氨酸激酶组成的受体复合体结合并传递信号，称为I型和II型。到目前为止，已经从哺乳动物中克隆了两个II型(ACTR-IIA，-IIB)和两个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转导生长、分化和凋亡中的作用，并获得了以下结果：(1)通过电穿孔技术建立了高表达ACTR-IA或ACTR-IB的HS-72细胞株。ACTR-IA的过表达抑制了激活素诱导的细胞周期停滞在G1期，这是由于视网膜母细胞瘤蛋白通过诱导细胞周期蛋白依赖的蛋白抑制因子p21的磷酸化而导致的细胞周期停滞，以及随后的细胞凋亡。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是彼此不同的…Follistain(激活素结合蛋白)可促进激活素与细胞表面硫酸乙酰肝素的结合。当细胞与活化素和卵泡刺激素共同孵育时，活化素的显著降解被硫酸肝素、氯喹和溶酶体蛋白酶抑制剂所阻断。这些结果表明，细胞相关的卵泡素能加速细胞对激活素的摄取，导致溶酶体酶的降解增加，从而在激活素清除系统中发挥作用。(3)为了了解卵泡素相关蛋白(FRP)在非洲爪哇胚胎发生中的作用，我们进行了整体原位杂交。在非洲爪哇胚胎的组织者区域，FRP的表达开始于第10阶段，这表明与卵泡抑素一样，FRP也是一种组织因子。在神经期至尾芽期，FRP在脊索和底板中有表达，提示其在神经结构的诱导中起作用。较少

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