Institute of Animal Genetics and Breeding, Sichuan Agricultural University, Ya'an, Sichuan, People's Republic of China.
PLoS One. 2012;7(7):e40250. doi: 10.1371/journal.pone.0040250. Epub 2012 Jul 6.
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.
糖原合酶激酶 3(GSK3α 和 GSK3β)是参与多种细胞过程和多种疾病的丝氨酸/苏氨酸激酶,包括情绪障碍、阿尔茨海默病、糖尿病和癌症。然而,在猪中,GSK3 的信息非常有限。鉴定和表征猪 GSK3 不仅对猪的遗传改良很重要,而且有助于理解和开发用于预防和治疗人类疾病的猪模型。
在猪的不同组织中鉴定出了 5 种不同的 GSK3β 同工型,其中 3 种是新的。这些同工型在猪不同组织的胎儿和成年期表现出不同的表达模式。在胰岛素处理过程中,GSK3β 同工型的 mRNA 表达水平受到差异调节,这表明不同的 GSK3β 同工型可能在胰岛素信号通路中具有不同的作用。此外,与其他 GSK3β 同工型相比,GSK3β5 在调节糖原合酶活性、磷酸化和猪 GYS1 和 GYS2 基因的表达方面具有不同的作用。
我们首次从猪的不同组织中报告了 5 种不同的 GSK3β 同工型。GSK3β 的剪接变体对糖原合酶表现出不同的活性。这些结果为 GSK3β 在调节糖原代谢中的作用提供了新的见解。