Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
PLoS One. 2010 Feb 3;5(2):e9029. doi: 10.1371/journal.pone.0009029.
Sik1 (salt inducible kinase 1) is a serine/threonine kinase that belongs to the stress- and energy-sensing AMP-activated protein kinase family. During murine embryogenesis, sik1 marks the monolayer of future myocardial cells that will populate first the primitive ventricle, and later the primitive atrium suggesting its involvement in cardiac cell differentiation and/or heart development. Despite that observation, the involvement of sik1 in cardiac differentiation is still unknown. We examined the sik1 function during cardiomyocyte differentiation using the ES-derived embryoid bodies. We produced a null embryonic stem cell using a gene-trap cell line carrying an insertion in the sik1 locus. In absence of the sik1 protein, the temporal appearance of cardiomyocytes is delayed. Expression profile analysis revealed sik1 as part of a genetic network that controls the cell cycle, where the cyclin-dependent kinase inhibitor p57(Kip2) is directly involved. Collectively, we provided evidence that sik1-mediated effects are specific for cardiomyogenesis regulating cardiomyoblast cell cycle exit toward terminal differentiation.
Sik1（盐诱导激酶 1）是一种丝氨酸/苏氨酸激酶，属于应激和能量感应 AMP 激活蛋白激酶家族。在小鼠胚胎发生过程中，sik1 标记未来心肌细胞的单层，这些细胞将首先填充原始心室，然后填充原始心房，表明其参与心脏细胞分化和/或心脏发育。尽管观察到了这一点，但 sik1 参与心脏分化的情况仍不清楚。我们使用 ES 衍生的胚状体研究了 sik1 在心肌细胞分化过程中的作用。我们使用携带 sik1 基因座插入的基因陷阱细胞系产生了一个 null 胚胎干细胞。在没有 sik1 蛋白的情况下，心肌细胞的出现时间延迟。表达谱分析表明 sik1 是控制细胞周期的遗传网络的一部分，其中细胞周期蛋白依赖性激酶抑制剂 p57（Kip2）直接参与其中。总之，我们提供的证据表明，sik1 介导的作用是针对心肌发生的，调节心肌细胞周期退出以进行终末分化。
