The role of activin binding protein in the activin signal transduction.

激活素是转化生长因子β大家族的成员，具有多种功能，包括刺激造血、旁分泌调节卵巢和睾丸功能、调节神经细胞分化和诱导爪蟾胚胎中的中胚层组织。为了了解激活素不同作用的表达机制，我们研究了激活素信号转导的分子机制，并获得了以下结果。(1)我们最近从小鼠胚胎癌（EC）细胞系P19中分离到激活素受体，发现激活素受体是一种跨膜丝氨酸/苏氨酸/酪氨酸蛋白激酶。在这项研究中，我们分离出小鼠激活素受体（II型）蛋白质COS细胞瞬时表达激活素受体（II型）DNA相同的亲和层析从ECP 19细胞。纯化的受体蛋白也被发现磷酸化本身和底物蛋白的丝氨酸，苏氨酸和泰 ...更多信息 松香残基。迄今为止，没有报道具有双重激酶活性的跨膜型激酶。因此，我们可以提出，激活素的信号转导采用了一种新的途径，通过一个新的类细胞受体。(2)我们通过FPLC凝胶过滤检测了激活素和卵泡抑素（激活素结合蛋白）之间的化学计量相互作用，发现卵泡抑素与激活素的摩尔比为2：1。通过测试激活素-卵泡抑素混合物对培养的垂体细胞的FSH释放的刺激或抑制作用也证实了该比率。这些结果表明，完全抑制1摩尔激活素的活性需要2摩尔卵泡抑素。此外，我们从猪卵巢中纯化了六种卵泡抑素分子形式。蛋白质化学分析表明，六种形式之间的结构差异是由C-末端区域的截短和/或糖链的存在引起的。发现所有六种分子具有相同的激活素结合活性。相比之下，C-末端截短形式显示出比C-末端延伸形式高得多的与大鼠颗粒细胞表面的亲和力。这些结果表明，细胞相关的卵泡抑素起着重要的作用，在控制激活素的各种行动，在旁分泌或自分泌的方式。少

Activins are members of a large family of transforming growth factors beta, and has various functions, including stimulation of hematopoiesis, paracrine regulation of ovarian and testicular function, modulation of nerve cell differentiation and induction of mesodermal tissues in Xenopus embryo. To understand the expression mechanism for diverse actions of activin, we investigated the molecular mechanism of activin signal transduction and obtained the following findings.(1) We have recently isolated the activin receptor from the mouse embryonal carcinoma (EC) cell line P19, and found that the activin receptor is a transmembrane serine/threonine/tyrosine protein kinase. In this study, we isolated a mouse activin receptor (type II) protein from COS cells transiently expressed the activin receptor (type II) DNA by the same affinity chromatography as from ECP19 cells. The purified receptor protein was also found to phosphorylate both itself and substrate proteins on serine, threonine and ty … More rosine residues. To date, no transmembrane-type kinase with dual kinase activity has been reported. Accordingly, we may propose that signal transduction of activin employs a novel pathway via a new class of cellular receptor.(2) We examined the stoichiometric interaction between activin and follistatin (activin-binding protein) by FPLC gel filtration, and found that the molar ratio of follistatin to activin was 2 : 1. This ratio was also confirmed by testing the stimulating or inhibiting effect of the activin-follistatin mixtures on FSH-release by cultured pituitary cells. These results indicate that two moles of follistatin is necessary for complete inhibition of the activity of one mole activin. Furthermore, we purified six molecular forms of follistatin from porcine ovaries. Protein chemical analysis revealed that the structural differences among the six forms were caused by truncation of the C-terminal region and/or the presence of carbohydrate chains. All six molecular species were found to have the same activin binding activity, By contrast, the C-terminal truncated form showed much higher affinity for tha rat granulosa cell surface than the C-terminal extended forms. These results suggest that cell-associated follstatin plays an important role in controlling the various actions of activin in a paracrine or autocrine manner. Less