Meyuhas Oded
Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
Int Rev Cell Mol Biol. 2008;268:1-37. doi: 10.1016/S1937-6448(08)00801-0.
The phosphorylation of ribosomal protein S6 (rpS6), which occurs in response to a wide variety of stimuli on five evolutionarily conserved serine residues, has attracted much attention since its discovery more than three decades ago. However, despite a large body of information on the respective kinases and the signal transduction pathways, the role of this phosphorylation remained obscure. It is only recent that targeting the genes encoding rpS6, the phosphorylatable serine residues or the respective kinases that the unique role of rpS6 and its posttranslational modification have started to be elucidated. This review focuses primarily on the critical role of rpS6 for mouse development, the pathways that transduce various signals into rpS6 phosphorylation, and the physiological functions of this modification. The mechanism(s) underlying the diverse effects of rpS6 phosphorylation on cellular and organismal physiology has yet to be determined. However, a model emerging from the currently available data suggests that rpS6 phosphorylation operates, at least partly, by counteracting positive signals simultaneously induced by rpS6 kinase, and thus might be involved in fine-tuning of the cellular response to these signals.
核糖体蛋白S6（rpS6）的磷酸化在五个进化保守的丝氨酸残基上发生，以响应多种刺激，自三十多年前被发现以来就备受关注。然而，尽管有大量关于各自激酶和信号转导途径的信息，但这种磷酸化的作用仍不清楚。直到最近，通过靶向编码rpS6的基因、可磷酸化的丝氨酸残基或各自的激酶，rpS6及其翻译后修饰的独特作用才开始得到阐明。本综述主要关注rpS6对小鼠发育的关键作用、将各种信号转导为rpS6磷酸化的途径以及这种修饰的生理功能。rpS6磷酸化对细胞和机体生理学产生多种影响的潜在机制尚未确定。然而，从目前可用数据中得出的一个模型表明，rpS6磷酸化至少部分地通过抵消rpS6激酶同时诱导的正向信号来发挥作用，因此可能参与对这些信号的细胞反应的微调。
