College of Pharmacy and Research Institute of Drug development, Chonnam National University, Gwangju 500-757, Republic of Korea.
Biochem Biophys Res Commun. 2011 Aug 5;411(3):637-41. doi: 10.1016/j.bbrc.2011.07.009. Epub 2011 Jul 12.
Osterix (Osx), a zinc-finger transcription factor is required for osteoblast differentiation and new bone formation during embryonic development. Akt is a member of the serine/threonine-specific protein kinase and plays important roles in osteoblast differentiation. The function of Osterix can be also modulated by post-translational modification. But, the precise molecular signaling mechanisms between Osterix and Akt are not known. In this study, we investigated the potential regulation of Osterix function by Akt in osteoblast differentiation. We found that Akt phosphorylates Osterix and that Akt activation increases protein stability, osteogenic activity and transcriptional activity of Osterix. We also found that BMP-2 increases the protein level of Osterix in an Akt activity-dependent manner. These results suggest that Akt activity enhances the osteogenic function of Osterix, at least in part, through protein stabilization and that BMP-2 regulates the osteogenic function of Osterix, at least in part, through Akt.
成骨细胞特异性转录因子 2（osterix，Osx）是胚胎发育过程中骨细胞分化和新骨形成所必需的。Akt 是丝氨酸/苏氨酸特异性蛋白激酶家族的一员，在成骨细胞分化中发挥重要作用。Osterix 的功能也可以通过翻译后修饰来调节。但是，Osterix 和 Akt 之间的确切分子信号机制尚不清楚。在这项研究中，我们研究了 Akt 在成骨细胞分化过程中对 Osterix 功能的潜在调节作用。我们发现 Akt 磷酸化 Osterix，并且 Akt 激活增加了 Osterix 的蛋白稳定性、成骨活性和转录活性。我们还发现 BMP-2 以 Akt 活性依赖性方式增加 Osterix 的蛋白水平。这些结果表明，Akt 活性至少部分通过蛋白稳定增强了 Osterix 的成骨功能，并且 BMP-2 至少部分通过 Akt 调节 Osterix 的成骨功能。
