Fission yeast TORC1 regulates phosphorylation of ribosomal S6 proteins in response to nutrients and its activity is inhibited by rapamycin
Fission yeast TORC1 regulates phosphorylation of ribosomal S6 proteins in response to nutrients and its activity is inhibited by rapamycin
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DOI：
10.1242/jcs.060319
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发表时间：
2010-03-01
影响因子：
4
通讯作者：
Tamanoi, Fuyuhiko
中科院分区：
文献类型：
--
作者：
Nakashima, Akio;Sato, Tatsuhiro;Tamanoi, Fuyuhiko
细胞活动受环境刺激通过蛋白质磷酸化调节。雷帕霉素靶蛋白（TOR）是一种丝氨酸/苏氨酸激酶，在细胞增殖和细胞生长中起着关键作用。在裂殖酵母中，含有Tor 2的TORC 1在营养响应中起着至关重要的作用。在这里，我们发现了一个氮调节磷蛋白，p27，在S。使用磷酸化Akt底物抗体检测粟酒裂殖酵母。p27磷酸化对氮供应的响应是由TORC 1和TSC-Rhb 1信号转导介导的，而不是由TORC 2或其他营养胁迫相关途径介导的。数据库和生化分析表明，p27是相同的核糖体蛋白S6（Rps 6）。Rps 6中的Ser 235和Ser 236是Rps 6被TORC 1磷酸化所必需的。这些Rps 6磷酸化对细胞活力是不利的。Rps 6磷酸化TORC 1也响应葡萄糖的可用性，并抑制渗透压和氧化应激。由于雷帕霉素-FKBP 12复合物与Tor 2中的FRB结构域的相互作用，雷帕霉素抑制TORC 1磷酸化Rps 6的能力。雷帕霉素还以TORC 1依赖性方式导致细胞大小减小。我们的研究结果表明，营养反应和雷帕霉素敏感的TORC 1-S6信号通路存在于S.粟酒裂殖酵母，并且该途径在细胞大小控制中发挥作用。
Cellular activities are regulated by environmental stimuli through protein phosphorylation. Target of rapamycin (TOR), a serine/threonine kinase, plays pivotal roles in cell proliferation and cell growth in response to nutrient status. In Schizosaccharomyces pombe, TORC1, which contains Tor2, plays crucial roles in nutrient response. Here we find a nitrogen-regulated phosphoprotein, p27, in S. pombe using the phospho-Akt substrate antibody. Response of p27 phosphorylation to nitrogen availability is mediated by TORC1 and the TSC-Rhb1 signaling, but not by TORC2 or other nutrient stress-related pathways. Database and biochemical analyses indicate that p27 is identical to ribosomal protein S6 (Rps6). Ser235 and Ser236 in Rps6 are necessary for Rps6 phosphorylation by TORC1. These Rps6 phosphorylations are dispensable for cell viability. Rps6 phosphorylation by TORC1 also responds to availability of glucose and is inhibited by osmotic and oxidative stresses. Rapamycin inhibits the ability of TORC1 to phosphorylate Rps6, owing to interaction of the rapamycin-FKBP12 complex with the FRB domain in Tor2. Rapamycin also leads to a decrease in cell size in a TORC1-dependent manner. Our findings demonstrate that the nutrient-responsive and rapamycin-sensitive TORC1-S6 signaling exists in S. pombe, and that this pathway plays a role in cell size control.