• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

HIV-1 Nef与肌醇三磷酸受体相互作用，以激活T细胞中的钙信号传导。

HIV-1 Nef interacts with inositol trisphosphate receptor to activate calcium signaling in T cells.

作者信息

Manninen Aki, Saksela Kalle

机构信息

Institute of Medical Technology, University of Tampere, Tampere FIN-33014, Finland.

出版信息

J Exp Med. 2002 Apr 15;195(8):1023-32. doi: 10.1084/jem.20012039.

DOI:10.1084/jem.20012039
PMID:11956293
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2193699/
Abstract

HIV-1 pathogenicity factor Nef has been shown to modulate calcium signaling in host cells, but the underlying molecular mechanisms have remained unclear. Here we show that calcium/calcineurin-dependent activation of nuclear factor of activated T cells (NFAT) by Nef in Jurkat T cells requires the endoplasmic reticulum-resident inositol trisphosphate receptor (IP(3)R), but yet does not involve increase in phospholipase-C gamma 1 (PLC gamma 1)-catalyzed production of IP(3) or depletion of IP(3)-regulated intracellular calcium stores. Nef could be coprecipitated with endogenous IP(3)R type-1 (IP(3)R1) from Nef-transfected Jurkat T cells as well as from HIV-infected primary human peripheral mononuclear cells. Thus, the Nef/IP(3)R1-interaction defines a novel T cell receptor-independent mechanism by which Nef can promote T cell activation, and appears to involve atypical IP(3)R-triggered activation of plasma membrane calcium influx channels in a manner that is uncoupled from depletion of intracellular calcium stores.

摘要

HIV-1致病因子Nef已被证明可调节宿主细胞中的钙信号传导，但其潜在的分子机制仍不清楚。在此我们表明，Nef在Jurkat T细胞中通过钙/钙调神经磷酸酶依赖性激活活化T细胞核因子（NFAT）需要内质网驻留的肌醇三磷酸受体（IP(3)R），但不涉及磷脂酶Cγ1（PLCγ1）催化产生IP(3)的增加或IP(3)调节的细胞内钙库的耗竭。Nef可与来自Nef转染的Jurkat T细胞以及HIV感染的原代人外周血单核细胞中的内源性1型IP(3)受体（IP(3)R1）共沉淀。因此，Nef/IP(3)R1相互作用定义了一种新的不依赖T细胞受体的机制，通过该机制Nef可促进T细胞活化，并且似乎涉及非典型的IP(3)R触发的质膜钙流入通道的激活，其方式与细胞内钙库的耗竭无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/2193699/7d059ae45780/012039f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/2193699/2b14d6bfff2b/012039f1a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/2193699/e0044df8d51c/012039f2a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/2193699/9a0caf92e91b/012039f3a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/2193699/15d86f6ebe71/012039f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/2193699/7d059ae45780/012039f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/2193699/2b14d6bfff2b/012039f1a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/2193699/e0044df8d51c/012039f2a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/2193699/9a0caf92e91b/012039f3a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/2193699/15d86f6ebe71/012039f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d72/2193699/7d059ae45780/012039f5.jpg

相似文献

1
HIV-1 Nef interacts with inositol trisphosphate receptor to activate calcium signaling in T cells.HIV-1 Nef与肌醇三磷酸受体相互作用，以激活T细胞中的钙信号传导。
J Exp Med. 2002 Apr 15;195(8):1023-32. doi: 10.1084/jem.20012039.
2
The hepatitis C virus core protein modulates T cell responses by inducing spontaneous and altering T-cell receptor-triggered Ca2+ oscillations.丙型肝炎病毒核心蛋白通过诱导自发的并改变T细胞受体触发的Ca2+振荡来调节T细胞反应。
J Biol Chem. 2003 May 23;278(21):18877-83. doi: 10.1074/jbc.M300185200. Epub 2003 Mar 13.
3
Synergistic activation of NFAT by HIV-1 nef and the Ras/MAPK pathway.HIV-1 Nef与Ras/MAPK途径对NFAT的协同激活作用。
J Biol Chem. 2000 Jun 2;275(22):16513-7. doi: 10.1074/jbc.M910032199.
4
Regulation of T cell activation by HIV-1 accessory proteins: Vpr acts via distinct mechanisms to cooperate with Nef in NFAT-directed gene expression and to promote transactivation by CREB.HIV-1辅助蛋白对T细胞活化的调控：Vpr通过不同机制发挥作用，在NFAT介导的基因表达中与Nef协同，并促进CREB介导的反式激活。
Virology. 2003 May 25;310(1):190-6. doi: 10.1016/s0042-6822(03)00164-8.
5
Hyper-responsiveness to stimulation of human immunodeficiency virus-infected CD4+ T cells requires Nef and Tat virus gene products and results from higher NFAT, NF-kappaB, and AP-1 induction.对人类免疫缺陷病毒感染的CD4+ T细胞刺激的高反应性需要Nef和Tat病毒基因产物，并且是由更高的NFAT、NF-κB和AP-1诱导产生的。
J Biol Chem. 2004 Sep 17;279(38):39520-31. doi: 10.1074/jbc.M407477200. Epub 2004 Jul 16.
6
Vav exchange factor counteracts the HIV-1 Nef-mediated decrease of plasma membrane GM1 and NF-AT activity in T cells.Vav交换因子可抵消HIV-1 Nef介导的T细胞膜表面GM1和NF-AT活性的降低。
Eur J Immunol. 2003 Aug;33(8):2186-96. doi: 10.1002/eji.200323682.
7
Human T-cell lymphotropic virus type 1 p12(I) expression increases cytoplasmic calcium to enhance the activation of nuclear factor of activated T cells.人类嗜T细胞病毒1型p12（I）的表达会增加细胞质钙含量，以增强活化T细胞核因子的激活。
J Virol. 2002 Oct;76(20):10374-82. doi: 10.1128/jvi.76.20.10374-10382.2002.
8
Inositol 1,4,5-trisphosphate directs Ca(2+) flow between mitochondria and the Endoplasmic/Sarcoplasmic reticulum: a role in regulating cardiac autonomic Ca(2+) spiking.肌醇1,4,5-三磷酸指导钙离子在线粒体与内质网/肌浆网之间流动：在调节心脏自主钙离子峰电位中的作用
Mol Biol Cell. 2000 May;11(5):1845-58. doi: 10.1091/mbc.11.5.1845.
9
Antisense-mediated loss of calcium homoeostasis endoplasmic reticulum protein (CHERP; ERPROT213-21) impairs Ca2+ mobilization, nuclear factor of activated T-cells (NFAT) activation and cell proliferation in Jurkat T-lymphocytes.反义介导的钙稳态内质网蛋白（CHERP；ERPROT213 - 21）缺失会损害Jurkat T淋巴细胞中的Ca2+动员、活化T细胞核因子（NFAT）激活及细胞增殖。
Biochem J. 2003 Jul 1;373(Pt 1):133-43. doi: 10.1042/BJ20030013.
10
Calcineurin is downstream of the inositol 1,4,5-trisphosphate receptor in the apoptotic and cell growth pathways.在凋亡和细胞生长途径中，钙调神经磷酸酶处于肌醇1,4,5-三磷酸受体的下游。
J Biol Chem. 2000 Mar 3;275(9):6417-20. doi: 10.1074/jbc.275.9.6417.

引用本文的文献

1
Lentiviral Nef Proteins Differentially Govern the Establishment of Viral Latency.慢病毒 Nef 蛋白差异调控病毒潜伏的建立。
J Virol. 2022 Apr 13;96(7):e0220621. doi: 10.1128/jvi.02206-21. Epub 2022 Mar 10.
2
Cal'MAM'ity at the Endoplasmic Reticulum-Mitochondrial Interface: A Potential Therapeutic Target for Neurodegeneration and Human Immunodeficiency Virus-Associated Neurocognitive Disorders.内质网-线粒体界面的“灾难”：神经退行性疾病和人类免疫缺陷病毒相关神经认知障碍的潜在治疗靶点。
Front Neurosci. 2021 Oct 21;15:715945. doi: 10.3389/fnins.2021.715945. eCollection 2021.
3
Modulation of Adaptive Immunity and Viral Infections by Ion Channels.

本文引用的文献

1
BANK regulates BCR-induced calcium mobilization by promoting tyrosine phosphorylation of IP(3) receptor.BANK通过促进IP(3)受体的酪氨酸磷酸化来调节BCR诱导的钙动员。
EMBO J. 2002 Jan 15;21(1-2):83-92. doi: 10.1093/emboj/21.1.83.
2
Nef triggers a transcriptional program in T cells imitating single-signal T cell activation and inducing HIV virulence mediators.Nef在T细胞中引发一个转录程序，模仿单信号T细胞激活并诱导HIV毒力介质。
Immunity. 2001 Jun;14(6):763-77. doi: 10.1016/s1074-7613(01)00158-3.
3
CaT1 manifests the pore properties of the calcium-release-activated calcium channel.
离子通道对适应性免疫和病毒感染的调节作用
Front Physiol. 2021 Oct 8;12:736681. doi: 10.3389/fphys.2021.736681. eCollection 2021.
4
HIV infection of astrocytes compromises inter-organelle interactions and inositol phosphate metabolism: A potential mechanism of bystander damage and viral reservoir survival.HIV 感染星形胶质细胞会损害细胞器间的相互作用和肌醇磷酸盐代谢：旁观者损伤和病毒储存库存活的潜在机制。
Prog Neurobiol. 2021 Nov;206:102157. doi: 10.1016/j.pneurobio.2021.102157. Epub 2021 Aug 26.
5
Dysregulation of host cell calcium signaling during viral infections: Emerging paradigm with high clinical relevance.病毒感染过程中宿主细胞钙信号的失调：具有高度临床相关性的新兴范例。
Mol Aspects Med. 2021 Oct;81:101004. doi: 10.1016/j.mam.2021.101004. Epub 2021 Jul 23.
6
Endoplasmic reticulum & mitochondrial calcium homeostasis: The interplay with viruses.内质网与线粒体钙离子稳态：与病毒的相互作用。
Mitochondrion. 2021 May;58:227-242. doi: 10.1016/j.mito.2021.03.008. Epub 2021 Mar 26.
7
Host Calcium Channels and Pumps in Viral Infections.病毒感染中的宿主钙通道和泵。
Cells. 2019 Dec 30;9(1):94. doi: 10.3390/cells9010094.
8
Implications of HIV-1 Nef for "Shock and Kill" Strategies to Eliminate Latent Viral Reservoirs.HIV-1 Nef 对消除潜伏病毒库的“休克和杀伤”策略的影响。
Viruses. 2018 Nov 30;10(12):677. doi: 10.3390/v10120677.
9
The TRPV4 channel links calcium influx to DDX3X activity and viral infectivity.TRPV4 通道将钙内流与 DDX3X 活性和病毒感染力联系起来。
Nat Commun. 2018 Jun 13;9(1):2307. doi: 10.1038/s41467-018-04776-7.
10
HIV-1 Nef Impairs the Formation of Calcium Membrane Territories Controlling the Signaling Nanoarchitecture at the Immunological Synapse.HIV-1 Nef蛋白损害钙膜区域的形成，而该区域控制着免疫突触处的信号纳米结构。
J Immunol. 2016 Nov 15;197(10):4042-4052. doi: 10.4049/jimmunol.1601132. Epub 2016 Oct 19.
CaT1表现出钙释放激活钙通道的孔道特性。
Nature. 2001 Apr 5;410(6829):705-9. doi: 10.1038/35070596.
4
Mechanism for down-regulation of CD28 by Nef.Nef下调CD28的机制。
EMBO J. 2001 Apr 2;20(7):1593-604. doi: 10.1093/emboj/20.7.1593.
5
Role of the phospholipase C-inositol 1,4,5-trisphosphate pathway in calcium release-activated calcium current and capacitative calcium entry.磷脂酶C-肌醇1,4,5-三磷酸途径在钙释放激活钙电流和容量性钙内流中的作用。
J Biol Chem. 2001 May 11;276(19):15945-52. doi: 10.1074/jbc.M011571200. Epub 2001 Feb 13.
6
Calcium signaling mechanisms in T lymphocytes.T淋巴细胞中的钙信号传导机制。
Annu Rev Immunol. 2001;19:497-521. doi: 10.1146/annurev.immunol.19.1.497.
7
HIV and SIV Nef modulate signal transduction and protein sorting in T cells.HIV和SIV的Nef蛋白可调节T细胞中的信号转导和蛋白质分选。
Cold Spring Harb Symp Quant Biol. 1999;64:453-63. doi: 10.1101/sqb.1999.64.453.
8
Activation of NFAT-dependent gene expression by Nef: conservation among divergent Nef alleles, dependence on SH3 binding and membrane association, and cooperation with protein kinase C-theta.Nef对NFAT依赖性基因表达的激活作用：不同Nef等位基因间的保守性、对SH3结合和膜结合的依赖性以及与蛋白激酶C-θ的协同作用
J Virol. 2001 Mar;75(6):3034-7. doi: 10.1128/JVI.75.6.3034-3037.2001.
9
Pleiotropic contributions of phospholipase C-gamma1 (PLC-gamma1) to T-cell antigen receptor-mediated signaling: reconstitution studies of a PLC-gamma1-deficient Jurkat T-cell line.磷脂酶C-γ1（PLC-γ1）对T细胞抗原受体介导信号传导的多效性作用：对PLC-γ1缺陷型Jurkat T细胞系的重建研究
Mol Cell Biol. 2000 Dec;20(24):9149-61. doi: 10.1128/MCB.20.24.9149-9161.2000.
10
Stable activation of single Ca2+ release-activated Ca2+ channels in divalent cation-free solutions.在无二价阳离子溶液中单个钙离子释放激活钙离子通道的稳定激活
J Biol Chem. 2001 Jan 12;276(2):1063-70. doi: 10.1074/jbc.M008348200.