SIK2参与TGFβ信号通路的调节

Positive Regulation of TGFβ Signal Pathway by SIK2

SIK2是调节糖脂代谢最重要的激酶之一.前期研究表明SIK2的同源家族成员SIK1可调控TGFβ信号通路的活性,但SIK2对TGFβ信号通路的调控作用尚无报导.本研究中我们检测了TGFβ通路对SIK2的调节作用以及SIK2对该通路活性的调控.结果表明,TGFβ刺激可诱导SIK2的mRNA表达上调;转染结合报告酶活性分析显示,SIK2可反式激活含TGFβ信号通路反应元件(CAGA)的人工启动子驱动的Luc报告基因的表达;在有TGFβ存在时甚至增强其表达;Western印迹分析表明TGFβ1诱导下敲低SIK2使p21蛋白表达水平下降.本研究结果显示SIK2可被TGFβ诱导表达,是一个新的TGFβ信号通路正调控因子.

S1K2, a kind of the kinases, plays a critical role in the metabolism of glucose and lipid. Previous studies suggest that S1K1, the homologous family member to SIK2, is involved in the regulation of TGFβ signaling pathway. However, the role of S1K2 in the regulation of this pathway remains unknown. In the present study, we found that the mRNA level of SIK2 is increased via TGFβ1 stimulation. The combination of transfection with reporter enzyme assays showed that SIK2 could transactivate the （CAGA）6-containing promoter, thereby driving the Luc reporter gene expression in the absence of TGFβ, even enhancing its expression in the presence of TGFβ. Western blotting analysis suggested that the protein level of p21 was decreased by SIK2 knockdown in the presence of TGFβ1. In conclusion, SIK2 is a novel positive regulator of TGFβ signal pathway, which can be induced by TGFβ1.