Meyuhas Oded
Department of Biochemistry and Molecular Biology, Institute for Medical Research - Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Int Rev Cell Mol Biol. 2015;320:41-73. doi: 10.1016/bs.ircmb.2015.07.006. Epub 2015 Aug 5.
The phosphorylation of ribosomal protein S6 (rpS6) has been described for the first time about four decades ago. Since then, numerous studies have shown that this modification occurs in response to a wide variety of stimuli on five evolutionarily conserved serine residues. However, despite a large body of information on the respective kinases and the signal transduction pathways, the physiological role of rpS6 phosphorylation remained obscure until genetic manipulations were applied in both yeast and mammals in an attempt to block this modification. Thus, studies based on both mice and cultured cells subjected to disruption of the genes encoding rpS6 and the respective kinases, as well as the substitution of the phosphorylatable serine residues in rpS6, have laid the ground for the elucidation of the multiple roles of this protein and its posttranslational modification. This review focuses primarily on newly identified kinases that phosphorylate rpS6, pathways that transduce various signals into rpS6 phosphorylation, and the recently established physiological functions of this modification. It should be noted, however, that despite the significant progress made in the last decade, the molecular mechanism(s) underlying the diverse effects of rpS6 phosphorylation on cellular and organismal physiology are still poorly understood.
核糖体蛋白S6（rpS6）的磷酸化大约在四十年前首次被描述。从那时起，大量研究表明，这种修饰发生在五个进化上保守的丝氨酸残基上，以响应各种各样的刺激。然而，尽管有大量关于相关激酶和信号转导途径的信息，但直到在酵母和哺乳动物中应用基因操作试图阻断这种修饰之前，rpS6磷酸化的生理作用仍然不清楚。因此，基于小鼠和培养细胞的研究，这些研究涉及编码rpS6和相关激酶的基因的破坏，以及rpS6中可磷酸化丝氨酸残基的替代，为阐明该蛋白及其翻译后修饰的多种作用奠定了基础。本综述主要关注新发现的使rpS6磷酸化的激酶、将各种信号转导为rpS6磷酸化的途径，以及这种修饰最近确立的生理功能。然而，应该指出的是，尽管在过去十年中取得了重大进展，但rpS6磷酸化对细胞和机体生理产生多种影响的分子机制仍知之甚少。
