Activin isoforms signal through type I receptor serine/threonine kinase ALK7
Activin isoforms signal through type I receptor serine/threonine kinase ALK7
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DOI：
10.1016/j.mce.2004.03.009
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发表时间：
2004-05-31
影响因子：
4.1
通讯作者：
Sugino, H
中科院分区：
文献类型：
--
作者：
Tsuchida, K;Nakatani, M;Sugino, H
激活素在细胞分化和发育中起着重要作用。激活素A信号是通过激活素II型受体（ActRIIs）和激活素IB型受体ALK4的联合介导的。其他激活素亚型的信号受体仍有待阐明。在这里。我们发现活化素AB和活化素B是ALK7的配体。ALK7是一个孤儿受体丝氨酸/苏氨酸激酶在包括胰岛在内的神经内分泌组织中表达。激活素AB和激活素B优先选择而非激活素A优先选择的ActRIIA和ALK7的结合，负责激活素介导的胰岛β细胞系MIN6分泌胰岛素。相反，所有激活素都能以不同水平的效力激活ActRIIA和ALK4的组合。因此，激活素信号通过I型受体的变化依赖于激活素同型和异型二聚体的组装。因此，受体异二聚体的不同组合介导了激活素异构体信号传导的变化。2004爱思唯尔爱尔兰有限公司版权所有。
Activins play a fundamental role in cell differentiation and development. Activin A signaling is mediated through a combination of activin type II receptors (ActRIIs) and the activin type IB receptor, ALK4. Signaling receptors of other activin isoforms remain to be elucidated. Here. we found that activin AB and activin B are ligands for ALK7. ALK7 is an orphan receptor serine/threonine kinase expressed in neuroendocrine tissues including pancreatic islets. The combination of ActRIIA and ALK7, preferred by activin AB and activin B but not by activin A, is responsible for activin-mediated secretion of insulin from pancreatic beta cell line, MIN6. In contrast, all activins activate a combination of ActRIIA and ALK4 with various levels of potency. Thus, variation in activin signaling through type I receptors is dependent upon homo- and heterodimeric assembly of activin isoforms. Thus, the differential combination of receptor heterodimers mediates variation in activin isoform signaling. (C) 2004 Elsevier Ireland Ltd. All rights reserved.