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生长激素对猪肝细胞中猪生长激素受体核定位的特异性诱导作用。

Growth hormone-specific induction of the nuclear localization of porcine growth hormone receptor in porcine hepatocytes.

作者信息

Lan H N, Hong P, Li R N, Shan A S, Zheng X

机构信息

College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, P. R. China.

College of Animal Science and Technology, Jilin Agricultural University, Changchun 130118, P. R. China.

出版信息

Domest Anim Endocrinol. 2017 Oct;61:39-47. doi: 10.1016/j.domaniend.2017.05.003. Epub 2017 Jun 8.

Abstract

The phenomenon of nuclear translocation of growth hormone receptor (GHR) in human, rat, and fish has been reported. To date, this phenomenon has not been described in a domestic animal (such as pig). In addition, the molecular mechanisms of GHR nuclear translocation have not been thoroughly elucidated. To this end, porcine hepatocytes were isolated and used as a cell model. We observed that porcine growth hormone (pGH) can induce porcine GHR's nuclear localization in porcine hepatocytes. Subsequently, the dynamics of pGH-induced pGHR's nuclear localization were analyzed and demonstrated that pGHR's nuclear localization occurs in a time-dependent manner. Next, we explored the mechanism of pGHR nuclear localization using different pGHR ligands, and we demonstrated that pGHR's nuclear translocation is GH(s)-dependent. We also observed that pGHR translocates into cell nuclei in a pGH dimerization-dependent fashion, whereas further experiments indicated that IMPα/β is involved in the nuclear translocation of the pGH-pGHR dimer. The pGH-pGHR dimer may form a pGH-GHR-JAK2 multiple complex in cell nuclei, which would suggest that similar to its function in the cell membrane, the nuclear-localized pGH-pGHR dimer might still have the ability to signal.

摘要

生长激素受体(GHR)在人、大鼠和鱼类中的核转位现象已有报道。迄今为止,这种现象在诸如猪等家畜中尚未被描述。此外,GHR核转位的分子机制尚未得到充分阐明。为此,分离猪肝细胞并将其用作细胞模型。我们观察到猪生长激素(pGH)可诱导猪肝细胞中猪GHR的核定位。随后,分析了pGH诱导的pGHR核定位的动力学,并证明pGHR的核定位呈时间依赖性。接下来,我们使用不同的pGHR配体探索了pGHR核定位的机制,并证明pGHR的核转位依赖于GH(s)。我们还观察到pGHR以pGH二聚化依赖的方式转位到细胞核中,而进一步的实验表明IMPα/β参与了pGH-pGHR二聚体的核转位。pGH-pGHR二聚体可能在细胞核中形成pGH-GHR-JAK2多聚复合物,这表明与其在细胞膜中的功能类似,核定位的pGH-pGHR二聚体可能仍然具有信号传导能力。

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