Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 200-701, Republic of Korea.
Biochem Biophys Res Commun. 2012 Feb 24;418(4):657-61. doi: 10.1016/j.bbrc.2012.01.071. Epub 2012 Jan 24.
The Down syndrome critical region 1 (DSCR1) gene encodes a regulator of the calcineurin 1 (RCAN1) protein, and the elevated levels of RCAN1 are associated with Alzheimer's disease (AD) and Down syndrome (DS). In this report, we found that protein kinase A (PKA) was able to phosphorylate RCAN1 in vitro and in vivo. In addition, we found that the phosphorylation of RCAN1 by PKA caused an increase of RCAN1 expression by increasing of the half-life of the protein. Consistently, the pharmacological inhibition of intracellular PKA using H-89 and the knockdown of the endogenous PKA catalytic subunit with siRNA decreased the expression of RCAN1. Furthermore, the phosphorylation of RCAN1 by PKA enhanced the inhibitory function of RCAN1 on calcineurin-mediated gene transcription. Our data provide the first evidence that PKA acts as an important regulatory component in the control of RCAN1 function through phosphorylation.
唐氏综合征关键区域 1（DSCR1）基因编码钙调神经磷酸酶 1（RCAN1）蛋白的调节剂，RCAN1 水平升高与阿尔茨海默病（AD）和唐氏综合征（DS）有关。在本报告中，我们发现蛋白激酶 A（PKA）能够在体外和体内使 RCAN1 磷酸化。此外，我们发现 PKA 对 RCAN1 的磷酸化通过增加蛋白质的半衰期引起 RCAN1 表达的增加。一致地，使用 H-89 抑制细胞内 PKA 和使用 siRNA 敲低内源性 PKA 催化亚基降低了 RCAN1 的表达。此外，PKA 对 RCAN1 的磷酸化增强了 RCAN1 对钙调神经磷酸酶介导的基因转录的抑制功能。我们的数据提供了第一个证据，表明 PKA 通过磷酸化作为控制 RCAN1 功能的重要调节成分。
