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草鱼脑垂体细胞中激活素 I 型和 II 型受体的分子克隆及其表达受激活素的差异调控。

Molecular cloning of activin type I and type II receptors and differential regulation of their expression by activin in grass carp pituitary cells.

机构信息

Key Laboratory for Neuroinformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, People's Republic of China.

出版信息

Gen Comp Endocrinol. 2010 Mar 1;166(1):211-6. doi: 10.1016/j.ygcen.2009.08.007. Epub 2009 Aug 21.

DOI:10.1016/j.ygcen.2009.08.007
PMID:19699739
Abstract

Activins, like other members of the transforming growth factor-beta superfamily, signal via two structurally related transmembrane serine/threonine kinase receptors classified as types II and I. Two cDNAs encoding activin type IIB receptor (ActRIIB) and activin type IB receptor (ActRIB) were cloned and characterized from grass carp. The deduced ActRIIB protein of 510 amino acids shared 79-90% identity with those in other vertebrates, while the predicted ActRIB protein of 505 amino acids exhibited high sequence identity (80-96%) to its counterparts in human, rat, mouse, frog, and zebrafish. Comparative analysis showed that both receptors contained the conserved amino acid residues required for ligand binding, and comprised the characteristic regions of an extracellular ligand binding domain, a single transmembrane region, and an intracellular serine/threonine kinase domain. Real-time PCR analysis revealed that both ActRIIB and ActRIB transcripts were ubiquitously expressed in all tissues examined, in particular with high expression levels in extra-gonadal tissues, including pituitary, brain, and liver. Using a static incubation approach, the feedback effects of exogenous activin on ActRIIB and ActRIB mRNA expression were examined at the pituitary level. Activin significantly stimulated ActRIB mRNA expression in a time- and dose-dependent manner, but had no effect on ActRIIB mRNA levels. These findings support the notion that activin receptors may serve as a local regulatory point involving in pituitary function of activin in fish.

摘要

激活素与转化生长因子-β超家族的其他成员一样,通过两种结构相关的跨膜丝氨酸/苏氨酸激酶受体(分类为 II 型和 I 型)传递信号。从草鱼中克隆并鉴定了编码激活素 IIB 受体(ActRIIB)和激活素 IB 受体(ActRIB)的两个 cDNA。推断的 510 个氨基酸的 ActRIIB 蛋白与其他脊椎动物的蛋白具有 79-90%的同源性,而预测的 505 个氨基酸的 ActRIB 蛋白与人类、大鼠、小鼠、青蛙和斑马鱼的对应蛋白具有高序列同一性(80-96%)。比较分析表明,这两种受体都含有与配体结合所需的保守氨基酸残基,并且包含特征区域,包括细胞外配体结合域、单一跨膜区域和细胞内丝氨酸/苏氨酸激酶域。实时 PCR 分析显示,ActRIIB 和 ActRIB 转录本在所有检测组织中均广泛表达,特别是在外生殖组织(包括垂体、脑和肝)中表达水平较高。采用静态孵育方法,在垂体水平上研究了外源性激活素对 ActRIIB 和 ActRIB mRNA 表达的反馈作用。激活素以时间和剂量依赖的方式显著刺激 ActRIB mRNA 的表达,但对 ActRIIB mRNA 水平没有影响。这些发现支持这样一种观点,即激活素受体可能作为一个局部调节点,参与鱼类中激活素对垂体功能的调节。

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