Fukada Haruhisa, Ozaki Yuichi, Pierce Andrew L, Adachi Shinji, Yamauchi Kohei, Hara Akihiko, Swanson Penny, Dickhoff Walton W
Northwest Fisheries Science Center, National Marine Fisheries Service, Seattle, Washington 98112, USA.
Endocrinology. 2005 May;146(5):2354-61. doi: 10.1210/en.2004-1578. Epub 2005 Feb 17.
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.
生长抑素（SL）是生长激素/催乳素（PRL）家族的一种垂体激素，迄今为止仅在鱼类中发现。与生长激素和催乳素相比，SL的一级结构在不同的鱼类物种中高度保守，这表明它具有重要功能以及限制结构变化的特异性受体。然而，人们对SL的功能了解甚少，并且尚未鉴定出SL的受体。在克隆鲑鱼生长激素受体cDNA的过程中，我们发现了一个变体，其与脊椎动物生长激素受体具有相对较高的序列同一性（38 - 58%），而与催乳素受体的同一性较低（28 - 33%）；然而，编码细胞外结构域的重组蛋白仅显示出对生长激素的微弱结合。该受体的重组细胞外结构域的配体结合证实，该cDNA编码的是SL的特异性受体。生长抑素受体（SLR）具有生长激素受体的共同特征，包括FGEFS基序、细胞外结构域中的六个半胱氨酸残基、一个单一的跨膜区域以及细胞内结构域中的Box 1和Box 2区域。这些结构特征使SLR属于I型细胞因子受体同二聚体组，该组包括生长激素、催乳素、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的受体。在11个组织中发现了SLR的转录本，其中肝脏和脂肪中的水平最高，这支持了SL的主要功能是调节脂质代谢这一观点。克隆SLR cDNA为发现鱼类中SL的新功能和靶组织，以及可能发现其他脊椎动物中该受体家族的新成员开辟了道路。
