Porcine IGF-1R synonymous mutations in the intracellular domain affect cell proliferation and alter kinase activity
Porcine IGF-1R synonymous mutations in the intracellular domain affect cell proliferation and alter kinase activity
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猪 IGF-1R 胞内结构域同义突变影响细胞增殖并改变激酶活性
DOI：
10.1016/j.ijbiomac.2020.02.281
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发表时间：
2020-06-01
影响因子：
8.2
通讯作者：
Hao, Linlin
中科院分区：
文献类型：
--
作者：
Wang, Chunli;Liu, Songcai;Hao, Linlin
小型猪被认为是异种器官移植的理想供体。阐明小型猪的形成机制具有重要意义。胰岛素样生长因子1受体（IGF-1 R）在细胞增殖和生物体生长的调节中至关重要。根据我们前期的研究，IGF-1 R在大型猪和小型猪肝脏和肌肉组织中的表达水平存在差异。本研究通过构建两种单倍型表达载体pcDNA3.1-LP（含大白色猪IGF-1 R ICD的CDS）和pcDNA3.1-BM（含巴纳香猪IGF-1 R ICD的CDS），分析了大小型猪IGF-1 R ICD的同义突变。BM组IGF-1 R在转录、翻译和自身磷酸化水平上的表达均低于LP组。BM组IGF-1 R对p-AICT/p-ERK蛋白表达的影响也明显低于LP组。检测PK-1 S和C2 C12细胞增殖情况，进一步了解该单倍型的功能。结果显示，BM组PK-15和C2 C12细胞增殖活性减弱。BM组mRNA和蛋白质的稳定性高于LP组。我们的数据表明，两个单倍型的IGF-IR CDS在ICD之间的大型和小型猪改变IGF-1 R的表达和下调AKT和ERK信号通路在翻译水平上，导致对PK-15和C2 C12细胞增殖的抑制作用。(C)2020爱思唯尔B. V.保留所有权利。
Miniature pigs are regarded as ideal organ donors for xenotransplantation into humans. Elucidating the formation mechanism of miniature pigs is important. The insulin-like growth factor 1 receptor (IGF-1R) is crucial in the regulation of cell proliferation and organismal growth. According to our previous research, the IGF-1R expression levels between large and miniature pigs showed different profiles in liver and muscle tissues. Here, live synonymous mutations of IGT-1R in the coding sequence (CDS) of intracellular domain (ICD) between large and miniature pigs were analysed by constructing expression vectors of two haplotypes and named pcDNA3.1-LP (with the CDS of IGF-1R ICD of Large White pigs, LP group) and pcDNA3.1-BM (with the CDS of IGF-1R ICD of Barna Xiang pigs, BM group). The IGF-1R of the BM group was expressed lower than that of the LP group in transcription, translation and autophosphorylation levels. The IGF-1R of the BM group also down-regulated the protein levels of p-AICT/p-ERK than that of the LP group. PK-1S and C2C12 cell proliferation were detected to further understand the function of the haplotype. Results showed that the proliferation viability of PK-15 and C2C12 cells weakened in the BM group. Moreover, the mRNA and protein stabilities of the BM group were higher than those of the LP group. Our data indicated that two haplotypes of IGF-IR CDS in ICD between large and miniature pigs altered IGF-1 R expression and down-regulated AKT and ERK signalling pathways at translation levels, resulting in an inhibitory effect on PK-15 and C2C12 cell proliferation. (C) 2020 Elsevier B.V. All rights reserved.