Ran结合蛋白3磷酸化将Ras和PI3激酶途径与核质运输联系起来。
Ran-binding protein 3 phosphorylation links the Ras and PI3-kinase pathways to nucleocytoplasmic transport.
作者信息
Yoon Sang-Oh, Shin Sejeong, Liu Yuzhen, Ballif Bryan A, Woo Michele S, Gygi Steven P, Blenis John
机构信息
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
出版信息
Mol Cell. 2008 Feb 15;29(3):362-75. doi: 10.1016/j.molcel.2007.12.024.
Abstract
The major participants of the Ras/ERK and PI3-kinase (PI3K) pathways are well characterized. The cellular response to activation of these pathways, however, can vary dramatically. How differences in signal strength, timing, spatial location, and cellular context promote specific cell-fate decisions remains unclear. Nuclear transport processes can have a major impact on the determination of cell fate; however, little is known regarding how nuclear transport is regulated by or regulates these pathways. Here we show that RSK and Akt, which are activated downstream of Ras/ERK and PI3K, respectively, modulate the Ran gradient and nuclear transport by interacting with, phosphorylating, and regulating Ran-binding protein 3 (RanBP3) function. Our findings highlight an important link between two major cell-fate determinants: nuclear transport and the Ras/ERK/RSK and PI3K/Akt signaling pathways.
摘要
Ras/ERK和PI3激酶（PI3K）信号通路的主要参与者已得到充分表征。然而，细胞对这些通路激活的反应可能有很大差异。信号强度、时间、空间位置和细胞环境的差异如何促进特定的细胞命运决定仍不清楚。核运输过程可能对细胞命运的决定产生重大影响；然而，关于核运输如何被这些通路调控或如何调控这些通路，我们知之甚少。在这里，我们表明，分别在Ras/ERK和PI3K下游被激活的RSK和Akt，通过与Ran结合蛋白3（RanBP3）相互作用、磷酸化并调节其功能，来调节Ran梯度和核运输。我们的研究结果突出了两个主要细胞命运决定因素之间的重要联系：核运输与Ras/ERK/RSK和PI3K/Akt信号通路。
相似文献
1
Ran-binding protein 3 phosphorylation links the Ras and PI3-kinase pathways to nucleocytoplasmic transport.Ran结合蛋白3磷酸化将Ras和PI3激酶途径与核质运输联系起来。
Mol Cell. 2008 Feb 15;29(3):362-75. doi: 10.1016/j.molcel.2007.12.024.
2
Ran is a potential therapeutic target for cancer cells with molecular changes associated with activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways.Ran 是一种潜在的治疗靶点，适用于那些具有与 PI3K/Akt/mTORC1 和 Ras/MEK/ERK 通路激活相关的分子变化的癌细胞。
Clin Cancer Res. 2012 Jan 15;18(2):380-91. doi: 10.1158/1078-0432.CCR-11-2035. Epub 2011 Nov 16.
3
AKT activation drives the nuclear localization of CSE1L and a pro-oncogenic transcriptional activation in ovarian cancer cells.AKT 的激活驱动 CSE1L 的核定位和卵巢癌细胞中的致癌转录激活。
Exp Cell Res. 2013 Oct 15;319(17):2627-36. doi: 10.1016/j.yexcr.2013.07.030. Epub 2013 Aug 13.
4
Ran-Binding Protein 3 Phosphorylation Links the Ras and PI3-Kinase Pathways to Nucleocytoplasmic Transport.Ran结合蛋白3磷酸化将Ras和PI3激酶途径与核质运输联系起来。
Mol Cell. 2023 Nov 16;83(22):4190. doi: 10.1016/j.molcel.2023.10.041.
5
The role of Ran-binding protein 3 during influenza A virus replication.Ran 结合蛋白 3 在甲型流感病毒复制过程中的作用。
J Gen Virol. 2013 May;94(Pt 5):977-984. doi: 10.1099/vir.0.049395-0. Epub 2013 Jan 9.
6
p90 ribosomal S6 kinase and p70 ribosomal S6 kinase link phosphorylation of the eukaryotic chaperonin containing TCP-1 to growth factor, insulin, and nutrient signaling.p90核糖体S6激酶和p70核糖体S6激酶将含TCP-1的真核伴侣蛋白的磷酸化与生长因子、胰岛素及营养信号传导联系起来。
J Biol Chem. 2009 May 29;284(22):14939-48. doi: 10.1074/jbc.M900097200. Epub 2009 Mar 30.
7
Signaling complexes and protein-protein interactions involved in the activation of the Ras and phosphatidylinositol 3-kinase pathways by the c-Ret receptor tyrosine kinase.c-Ret受体酪氨酸激酶激活Ras和磷脂酰肌醇3-激酶途径所涉及的信号复合物及蛋白质-蛋白质相互作用。
J Biol Chem. 2000 Dec 15;275(50):39159-66. doi: 10.1074/jbc.M006908200.
8
Both src-dependent and -independent mechanisms mediate phosphatidylinositol 3-kinase regulation of colony-stimulating factor 1-activated mitogen-activated protein kinases in myeloid progenitors.src依赖性和非依赖性机制均介导磷脂酰肌醇3激酶对髓系祖细胞中集落刺激因子1激活的丝裂原活化蛋白激酶的调节。
Mol Cell Biol. 2000 Sep;20(18):6779-98. doi: 10.1128/MCB.20.18.6779-6798.2000.
9
Recruitment of the extracellular signal-regulated kinase/ribosomal S6 kinase signaling pathway to the NFATc4 transcription activation complex.细胞外信号调节激酶/核糖体S6激酶信号通路募集至NFATc4转录激活复合物。
Mol Cell Biol. 2005 Feb;25(3):907-20. doi: 10.1128/MCB.25.3.907-920.2005.
10
Phosphatidylinositol 3-kinase requirement in activation of the ras/C-raf-1/MEK/ERK and p70(s6k) signaling cascade by the insulinomimetic agent vanadyl sulfate.胰岛素模拟剂硫酸氧钒激活ras/C-raf-1/MEK/ERK和p70(s6k)信号级联反应中对磷脂酰肌醇3激酶的需求
Biochemistry. 1999 Nov 2;38(44):14667-75. doi: 10.1021/bi9911886.
引用本文的文献
1
Positive Regulation of Cellular Proteins by Influenza Virus for Productive Infection.流感病毒对细胞蛋白的正向调节以实现有效感染
Int J Mol Sci. 2025 Apr 10;26(8):3584. doi: 10.3390/ijms26083584.
2
Age-dependent decline in remyelination capacity is mediated by apelin-APJ signaling.年龄相关的髓鞘再生能力下降是由阿片肽-APJ 信号介导的。
Nat Aging. 2021 Mar;1(3):284-294. doi: 10.1038/s43587-021-00041-7. Epub 2021 Mar 15.
3
Ran GTPase and Its Importance in Cellular Signaling and Malignant Phenotype.Ran GTPase 及其在细胞信号转导和恶性表型中的重要性。
Int J Mol Sci. 2023 Feb 4;24(4):3065. doi: 10.3390/ijms24043065.
4
Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS.COVID-19 和细菌性败血症引起的 ARDS 的多组学比较分析。
PLoS Pathog. 2022 Sep 19;18(9):e1010819. doi: 10.1371/journal.ppat.1010819. eCollection 2022 Sep.
5
Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS.新型冠状病毒肺炎与细菌性脓毒症诱导的急性呼吸窘迫综合征的多组学比较分析
medRxiv. 2022 Aug 13:2022.05.16.22274587. doi: 10.1101/2022.05.16.22274587.
6
β-Arrestin2 Is Critically Involved in the Differential Regulation of Phosphosignaling Pathways by Thyrotropin-Releasing Hormone and Taltirelin.β- arrestin2 在促甲状腺素释放激素和塔尔替林对磷酸信号通路的差异调节中起关键作用。
Cells. 2022 Apr 27;11(9):1473. doi: 10.3390/cells11091473.
7
RanBP3 Regulates Proliferation, Apoptosis and Chemosensitivity of Chronic Myeloid Leukemia Cells Mediating SMAD2/3 and ERK1/2 Nuclear Transport.RanBP3通过介导SMAD2/3和ERK1/2核转运来调节慢性粒细胞白血病细胞的增殖、凋亡和化疗敏感性。
Front Oncol. 2021 Aug 24;11:698410. doi: 10.3389/fonc.2021.698410. eCollection 2021.
8
Regulation of nuclear mTORC1.细胞核中mTORC1的调控
Mol Cell Oncol. 2021 May 5;8(3):1896348. doi: 10.1080/23723556.2021.1896348. eCollection 2021.
9
Biochemical Activity Architectures Visualized-Using Genetically Encoded Fluorescent Biosensors to Map the Spatial Boundaries of Signaling Compartments.生物化学活性结构可视化——利用基因编码荧光生物传感器绘制信号隔室的空间边界。
Acc Chem Res. 2021 May 18;54(10):2409-2420. doi: 10.1021/acs.accounts.1c00056. Epub 2021 May 5.
10
Location-specific inhibition of Akt reveals regulation of mTORC1 activity in the nucleus.特异性抑制 Akt 揭示了 mTORC1 活性在核内的调节。
Nat Commun. 2020 Nov 30;11(1):6088. doi: 10.1038/s41467-020-19937-w.
本文引用的文献
1
Controlling protein compartmentalization to overcome disease.控制蛋白质区室化以战胜疾病。
Pharm Res. 2007 Jan;24(1):17-27. doi: 10.1007/s11095-006-9133-z. Epub 2006 Sep 13.
2
Ras, PI(3)K and mTOR signalling controls tumour cell growth.Ras、磷脂酰肌醇-3激酶（PI(3)K）和哺乳动物雷帕霉素靶蛋白（mTOR）信号传导控制肿瘤细胞生长。
Nature. 2006 May 25;441(7092):424-30. doi: 10.1038/nature04869.
3
MAPK signal specificity: the right place at the right time.丝裂原活化蛋白激酶信号特异性：在正确的时间处于正确的位置。
Trends Biochem Sci. 2006 May;31(5):268-75. doi: 10.1016/j.tibs.2006.03.009. Epub 2006 Apr 17.
4
The view from Awaji island: past, present, and future of RCC1 and the Ran GTPase system.淡路岛之展望：RCC1与Ran GTP酶系统的过去、现在与未来
Dev Cell. 2005 Dec;9(6):729-33. doi: 10.1016/j.devcel.2005.11.010.
5
Exploiting the PI3K/AKT pathway for cancer drug discovery.利用PI3K/AKT信号通路进行癌症药物研发。
Nat Rev Drug Discov. 2005 Dec;4(12):988-1004. doi: 10.1038/nrd1902.
6
The tumor suppressor DAP kinase is a target of RSK-mediated survival signaling.肿瘤抑制因子DAP激酶是RSK介导的生存信号的一个靶点。
Curr Biol. 2005 Oct 11;15(19):1762-7. doi: 10.1016/j.cub.2005.08.050.
7
The Crm de la crème of mitosis.有丝分裂中的精华。
Nat Cell Biol. 2005 Jun;7(6):551-2. doi: 10.1038/ncb0605-551.
8
Crm1 is a mitotic effector of Ran-GTP in somatic cells.Crm1是体细胞中Ran-GTP的有丝分裂效应因子。
Nat Cell Biol. 2005 Jun;7(6):626-32. doi: 10.1038/ncb1263.
9
The tRNA methylase METTL1 is phosphorylated and inactivated by PKB and RSK in vitro and in cells.转运RNA甲基化酶METTL1在体外和细胞中被蛋白激酶B（PKB）和核糖体S6激酶（RSK）磷酸化并失活。
EMBO J. 2005 May 4;24(9):1696-705. doi: 10.1038/sj.emboj.7600648. Epub 2005 Apr 14.
10
Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase.促肿瘤佛波酯和活化的Ras通过p90核糖体S6激酶使结节性硬化肿瘤抑制复合物失活。
Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13489-94. doi: 10.1073/pnas.0405659101. Epub 2004 Sep 1.
Zotero 插件