Alternative splicing of the porcine glycogen synthase kinase 3β (GSK-3β) gene with differential expression patterns and regulatory functions.
Alternative splicing of the porcine glycogen synthase kinase 3β (GSK-3β) gene with differential expression patterns and regulatory functions.
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DOI：
10.1371/journal.pone.0040250
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Xiong Y
中科院分区：
文献类型：
--
作者：
Wang L;Zuo B;Xu D;Ren Z;Zhang H;Li X;Lei M;Xiong Y
糖原合成酶激酶3（GSK 3 α和GSK 3 β）是丝氨酸/苏氨酸激酶，参与许多细胞过程和多种疾病，包括情绪障碍、阿尔茨海默病、糖尿病和癌症。然而，在猪中，有关GSK 3的信息非常有限。猪GSK 3基因的鉴定和鉴定不仅对猪的遗传改良具有重要意义，而且有助于理解和开发用于人类疾病预防和治疗的猪模型。在猪的不同组织中发现了5种不同的GSK 3 β亚型，其中3种亚型为新亚型。这些异构体在猪胚胎和成体不同组织中具有不同的表达模式。在胰岛素治疗过程中，GSK 3 β亚型mRNA表达水平的变化存在差异，提示不同的GSK 3 β亚型在胰岛素信号通路中可能具有不同的作用。此外，GSK 3 β5对猪糖原合成酶活性、磷酸化及GYS 1和GYS 2基因表达的调控作用与其他GSK 3 β亚型不同。我们首次报道了从猪不同组织中鉴定出的5种不同的GSK 3 β亚型。GSK 3 β的剪接变体对糖原合酶表现出不同的活性。这些结果为研究GSK 3 β在调节糖原代谢中的作用提供了新的思路。
Glycogen synthase kinase 3 (GSK3α and GSK3β) are serine/threonine kinases involved in numerous cellular processes and diverse diseases including mood disorders, Alzheimer’s disease, diabetes, and cancer. However, in pigs, the information on GSK3 is very limited. Identification and characterization of pig GSK3 are not only important for pig genetic improvement, but also contribute to the understanding and development of porcine models for human disease prevention and treatment. Five different isoforms of GSK3β were identified in porcine different tissues, in which three isoforms are novel. These isoforms had differential expression patterns in the fetal and adult of the porcine different tissues. The mRNA expression level of GSK3β isoforms was differentially regulated during the course of the insulin treatment, suggesting that different GSK3β isoforms may have different roles in insulin signaling pathway. Moreover, GSK3β5 had a different role on regulating the glycogen synthase activity, phosphorylation and the expression of porcine GYS1 and GYS2 gene compared to other GSK3β isoforms. We are the first to report five different isoforms of GSK3β identified from the porcine different tissues. Splice variants of GSK3β exhibit differential activity towards glycogen synthase. These results provide new insight into roles of the GSK3β on regulating glycogen metabolism.