Identification of the salmon somatolactin receptor, a new member of the cytokine receptor family
Identification of the salmon somatolactin receptor, a new member of the cytokine receptor family
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DOI：
10.1210/en.2004-1578
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发表时间：
2005-05-01
期刊：
影响因子：
4.8
通讯作者：
Dickhoff, WW
中科院分区：
文献类型：
--
作者：
Fukada, H;Ozaki, Y;Dickhoff, WW
生长肌动素（SL）是生长激素/催乳素（PRL）家族中的一种垂体激素，迄今为止仅在鱼类中发现。与GH和PRL相比，SL的初级结构在不同鱼类中高度保守，表明它具有重要的功能和限制结构变化的鉴别受体。然而，人们对SL的功能知之甚少，SL的受体尚未确定。在克隆三文鱼生长激素受体cDNA的过程中，我们发现了一个与脊椎动物生长激素受体同源性较高（38 - 58%）、与PRL受体同源性较低（28 - 33%）的突变体；而编码胞外结构域的重组蛋白与生长激素的结合较弱。该受体的配体结合证实了该cDNA编码了SL特异性受体。SL受体（SLR）具有GH受体的共同特征，包括FGEFS基序、胞外区域的6个半胱氨酸残基、单个跨膜区域以及胞内区域的Box 1和Box 2区域。这些结构特征使SLR属于细胞因子受体I型同型二聚体组，该组包括生长激素、PRL、促红细胞生成素、血小板生成素、粒细胞集落刺激因子和瘦素受体。SLR的转录本在肝脏和脂肪中最高的11个组织中被发现，支持了SL的主要功能是调节脂质代谢的观点。克隆SLR cDNA为在鱼类中发现新的SL功能和靶组织开辟了道路，并可能在其他脊椎动物中发现该受体家族的新成员。
Somatolactin (SL) is a pituitary hormone of the GH/prolactin (PRL) family that so far has been found only in fish. Compared with GH and PRL, the primary structure of SL is highly conserved among divergent fish species, suggesting it has an important function and a discriminating receptor that constrains structural change. However, SL functions are poorly understood, and receptors for SL have not yet been identified. During cloning of GH receptor cDNA from salmon, we found a variant with relatively high ( 38 - 58%) sequence identity to vertebrate GH receptors and low ( 28 - 33%) identity to PRL receptors; however, the recombinant protein encoding the extracellular domain showed only weak binding of GH. Ligand binding of the recombinant extracellular domain for this receptor confirmed that the cDNA encoded a specific receptor for SL. The SL receptor (SLR) has common features of a GH receptor including FGEFS motif, six cysteine residues in the extracellular domain, a single transmembrane region, and Box 1 and 2 regions in the intracellular domain. These structural characteristics place the SLR in the cytokine receptor type I homodimeric group, which includes receptors for GH, PRL, erythropoietin, thrombopoietin, granulocyte-colony stimulating factor, and leptin. Transcripts for SLR were found in 11 tissues with highest levels in liver and fat, supporting the notion that a major function of SL is regulation of lipid metabolism. Cloning SLR cDNA opens the way for discovery of new SL functions and target tissues in fish, and perhaps novel members of this receptor family in other vertebrates.