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1
Targeted disruption of p70(s6k) defines its role in protein synthesis and rapamycin sensitivity.p70核糖体蛋白S6激酶（p70(s6k)）的靶向破坏确定了其在蛋白质合成和雷帕霉素敏感性中的作用。
Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5033-8. doi: 10.1073/pnas.95.9.5033.
2
RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1.翻译调节因子p70 S6激酶和4E-BP1的RAFT1磷酸化作用
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3
Inhibition of insulin signaling and adipogenesis by rapamycin: effect on phosphorylation of p70 S6 kinase vs eIF4E-BP1.雷帕霉素对胰岛素信号传导和脂肪生成的抑制作用：对p70 S6激酶与eIF4E-BP1磷酸化的影响
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4
Regulation of protein synthesis by cholecystokinin in rat pancreatic acini involves PHAS-I and the p70 S6 kinase pathway.胆囊收缩素对大鼠胰腺腺泡蛋白质合成的调节涉及PHAS-I和p70 S6激酶途径。
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The role of c-Myc on granulocyte colony-stimulating factor-dependent neutrophilic proliferation and differentiation of HL-60 cells.c-Myc在粒细胞集落刺激因子依赖的HL-60细胞嗜中性粒细胞增殖和分化中的作用。
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Protein phosphatase 2A interacts with the 70-kDa S6 kinase and is activated by inhibition of FKBP12-rapamycinassociated protein.蛋白磷酸酶2A与70 kDa的S6激酶相互作用，并通过抑制FKBP12-雷帕霉素相关蛋白而被激活。
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Translational homeostasis: eukaryotic translation initiation factor 4E control of 4E-binding protein 1 and p70 S6 kinase activities.翻译后稳态：真核生物翻译起始因子4E对4E结合蛋白1和p70 S6激酶活性的调控
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p70(s6k) integrates phosphatidylinositol 3-kinase and rapamycin-regulated signals for E2F regulation in T lymphocytes.p70核糖体蛋白S6激酶整合磷脂酰肌醇3激酶和雷帕霉素调节的信号，用于T淋巴细胞中E2F的调节。
Mol Cell Biol. 1999 Jul;19(7):4729-38. doi: 10.1128/MCB.19.7.4729.
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Cloning and characterization of p70(S6K beta) defines a novel family of p70 S6 kinases.p70（S6Kβ）的克隆与特性分析确定了一个新的p70 S6激酶家族。
Biochem Biophys Res Commun. 1998 Dec 18;253(2):470-6. doi: 10.1006/bbrc.1998.9784.

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本文引用的文献

1
The insulin-induced signalling pathway leading to S6 and initiation factor 4E binding protein 1 phosphorylation bifurcates at a rapamycin-sensitive point immediately upstream of p70s6k.导致核糖体蛋白S6和真核翻译起始因子4E结合蛋白1磷酸化的胰岛素诱导信号通路在p70核糖体蛋白S6激酶上游紧邻的一个雷帕霉素敏感位点处发生分支。
Mol Cell Biol. 1997 Sep;17(9):5426-36. doi: 10.1128/MCB.17.9.5426.
2
Rapamycin suppresses 5'TOP mRNA translation through inhibition of p70s6k.雷帕霉素通过抑制p70s6k来抑制5'TOP mRNA的翻译。
EMBO J. 1997 Jun 16;16(12):3693-704. doi: 10.1093/emboj/16.12.3693.
3
Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin.雷帕霉素哺乳动物靶点对翻译抑制因子PHAS-I的磷酸化作用
Science. 1997 Jul 4;277(5322):99-101. doi: 10.1126/science.277.5322.99.
4
Rapamycin-sensitive phosphorylation of ribosomal protein S17 by p70 S6 kinase.p70 S6激酶对核糖体蛋白S17的雷帕霉素敏感磷酸化作用。
Biochem Biophys Res Commun. 1996 Oct 14;227(2):507-12. doi: 10.1006/bbrc.1996.1537.
5
A signaling pathway to translational control.一条通向翻译控制的信号通路。
Cell. 1996 Aug 23;86(4):517-20. doi: 10.1016/s0092-8674(00)80125-7.
6
4E-BP1 phosphorylation is mediated by the FRAP-p70s6k pathway and is independent of mitogen-activated protein kinase.4E-BP1磷酸化由FRAP-p70s6k途径介导，且不依赖于丝裂原活化蛋白激酶。
Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4076-80. doi: 10.1073/pnas.93.9.4076.
7
Rapamycin blocks the phosphorylation of 4E-BP1 and inhibits cap-dependent initiation of translation.雷帕霉素可阻断4E-BP1的磷酸化，并抑制帽依赖性翻译起始。
EMBO J. 1996 Feb 1;15(3):658-64.
8
p70s6k function is essential for G1 progression.p70s6k功能对于G1期进程至关重要。
Nature. 1993 May 13;363(6425):170-2. doi: 10.1038/363170a0.
9
Failure of rapamycin to block proliferation once resting cells have entered the cell cycle despite inactivation of p70 S6 kinase.尽管p70 S6激酶失活，但一旦静止细胞进入细胞周期，雷帕霉素仍无法阻止其增殖。
J Biol Chem. 1993 Jun 5;268(16):12062-8.
10
Rapamycin selectively represses translation of the "polypyrimidine tract" mRNA family.雷帕霉素选择性抑制“多嘧啶序列”mRNA家族的翻译。
Proc Natl Acad Sci U S A. 1994 May 10;91(10):4441-5. doi: 10.1073/pnas.91.10.4441.

p70核糖体蛋白S6激酶（p70(s6k)）的靶向破坏确定了其在蛋白质合成和雷帕霉素敏感性中的作用。

Targeted disruption of p70(s6k) defines its role in protein synthesis and rapamycin sensitivity.

作者信息

Kawasome H, Papst P, Webb S, Keller G M, Johnson G L, Gelfand E W, Terada N

机构信息

Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.

出版信息

Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5033-8. doi: 10.1073/pnas.95.9.5033.

DOI:10.1073/pnas.95.9.5033
PMID:9560223
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC20208/
Abstract

Here, we disrupted the p70 S6 kinase (p70(s6k)) gene in murine embryonic stem cells to determine the role of this kinase in cell growth, protein synthesis, and rapamycin sensitivity. p70(s6k-/-) cells proliferated at a slower rate than parental cells, suggesting that p70(s6k) has a positive influence on cell proliferation but is not essential. In addition, rapamycin inhibited proliferation of p70(s6k-/-) cells, indicating that other events inhibited by the drug, independent of p70(s6k), also are important for both cell proliferation and the action of rapamycin. In p70(s6k-/-) cells, which exhibited no ribosomal S6 phosphorylation, translation of mRNA encoding ribosomal proteins was not increased by serum nor specifically inhibited by rapamycin. In contrast, rapamycin inhibited phosphorylation of initiation factor 4E-binding protein 1 (4E-BP1), general mRNA translation, and overall protein synthesis in p70(s6k-/-) cells, indicating that these events proceed independently of p70(s6k) activity. This study localizes the function of p70(s6k) to ribosomal biogenesis by regulating ribosomal protein synthesis at the level of mRNA translation.

摘要

在此，我们在小鼠胚胎干细胞中破坏了p70 S6激酶（p70(s6k)）基因，以确定该激酶在细胞生长、蛋白质合成和雷帕霉素敏感性中的作用。p70(s6k-/-)细胞的增殖速度比亲代细胞慢，这表明p70(s6k)对细胞增殖有积极影响，但并非必不可少。此外，雷帕霉素抑制了p70(s6k-/-)细胞的增殖，这表明该药物抑制的其他事件，独立于p70(s6k)，对细胞增殖和雷帕霉素的作用也很重要。在没有核糖体S6磷酸化的p70(s6k-/-)细胞中，编码核糖体蛋白的mRNA的翻译既不会因血清而增加，也不会被雷帕霉素特异性抑制。相反，雷帕霉素抑制了p70(s6k-/-)细胞中起始因子4E结合蛋白1（4E-BP1）的磷酸化、一般mRNA翻译和整体蛋白质合成，这表明这些事件独立于p70(s6k)活性进行。本研究通过在mRNA翻译水平上调节核糖体蛋白合成，将p70(s6k)的功能定位到核糖体生物发生上。