Fernandez-Alonso Rosalia, Bustos Francisco, Williams Charles A C, Findlay Greg M
The MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, The University of Dundee, Dundee DD1 5EH, UK.
The MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, The University of Dundee, Dundee DD1 5EH, UK.
J Mol Biol. 2017 May 19;429(10):1504-1520. doi: 10.1016/j.jmb.2017.04.013. Epub 2017 Apr 26.
Post-translational modification of proteins by phosphorylation plays a key role in regulating all aspects of eukaryotic biology. Embryonic stem cell (ESC) pluripotency, defined as the ability to differentiate into all cell types in the adult body, is no exception. Maintenance and dissolution of pluripotency are tightly controlled by phosphorylation. As a result, key signalling pathways that regulate pluripotency have been identified and their functions well characterised. Amongst the best studied are the fibroblast growth factor (FGF)-ERK1/2 pathway, PI3K-AKT, the leukemia inhibitory factor (LIF)-JAK-STAT3 axis, Wnt-GSK3 signalling, and the transforming growth factor (TGF)β family. However, these kinase pathways constitute only a small proportion of the protein kinase complement of pluripotent cells, and there is accumulating evidence that diverse phosphorylation systems modulate ESC pluripotency. Here, we review recent progress in understanding the overarching role of phosphorylation in mediating communication from the cellular environment, metabolism, and cell cycle to the core pluripotency machinery.
蛋白质的磷酸化翻译后修饰在调节真核生物生物学的各个方面发挥着关键作用。胚胎干细胞（ESC）的多能性，即分化为成体中所有细胞类型的能力，也不例外。多能性的维持和解除受到磷酸化的严格控制。因此，已经确定了调节多能性的关键信号通路，并对其功能进行了充分表征。其中研究得最深入的是成纤维细胞生长因子（FGF）-ERK1/2通路、PI3K-AKT、白血病抑制因子（LIF）-JAK-STAT3轴、Wnt-GSK3信号传导以及转化生长因子（TGF）β家族。然而，这些激酶通路仅占多能细胞蛋白激酶补体的一小部分，并且越来越多的证据表明，多种磷酸化系统调节胚胎干细胞的多能性。在这里，我们综述了在理解磷酸化在介导从细胞环境、代谢和细胞周期到核心多能性机制的通讯中的总体作用方面的最新进展。
