• 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

磷脂酰肌醇-3,4,5-三磷酸（PI(3,4,5)P3）和磷脂酰肌醇-4,5-二磷酸（PI(4,5)P2）脂质通过多碱性簇将蛋白质靶向到质膜。

PI(3,4,5)P3 and PI(4,5)P2 lipids target proteins with polybasic clusters to the plasma membrane.

作者信息

Heo Won Do, Inoue Takanari, Park Wei Sun, Kim Man Lyang, Park Byung Ouk, Wandless Thomas J, Meyer Tobias

机构信息

Department of Molecular Pharmacology, 318 Campus Drive, Clark Building, Stanford University Medical School, Stanford, CA 94305, USA.

出版信息

Science. 2006 Dec 1;314(5804):1458-61. doi: 10.1126/science.1134389. Epub 2006 Nov 9.

DOI:10.1126/science.1134389
PMID:17095657
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3579512/
Abstract

Many signaling, cytoskeletal, and transport proteins have to be localized to the plasma membrane (PM) in order to carry out their function. We surveyed PM-targeting mechanisms by imaging the subcellular localization of 125 fluorescent protein-conjugated Ras, Rab, Arf, and Rho proteins. Out of 48 proteins that were PM-localized, 37 contained clusters of positively charged amino acids. To test whether these polybasic clusters bind negatively charged phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] lipids, we developed a chemical phosphatase activation method to deplete PM PI(4,5)P2. Unexpectedly, proteins with polybasic clusters dissociated from the PM only when both PI(4,5)P2 and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] were depleted, arguing that both lipid second messengers jointly regulate PM targeting.

摘要

许多信号转导、细胞骨架和转运蛋白必须定位于质膜（PM）才能发挥其功能。我们通过对125种荧光蛋白偶联的Ras、Rab、Arf和Rho蛋白的亚细胞定位进行成像，研究了质膜靶向机制。在48种定位于质膜的蛋白中，有37种含有带正电荷的氨基酸簇。为了测试这些多碱性簇是否结合带负电荷的磷脂酰肌醇4,5-二磷酸[PI(4,5)P2]脂质，我们开发了一种化学磷酸酶激活方法来耗尽质膜PI(4,5)P2。出乎意料的是，只有当PI(4,5)P2和磷脂酰肌醇3,4,5-三磷酸[PI(3,4,5)P3]都被耗尽时，带有多碱性簇的蛋白才会从质膜上解离，这表明这两种脂质第二信使共同调节质膜靶向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b31d/3579512/436e838e8b88/nihms180886f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b31d/3579512/1fd27fc0d080/nihms180886f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b31d/3579512/6c1754baa520/nihms180886f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b31d/3579512/5cf26808bdb2/nihms180886f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b31d/3579512/436e838e8b88/nihms180886f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b31d/3579512/1fd27fc0d080/nihms180886f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b31d/3579512/6c1754baa520/nihms180886f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b31d/3579512/5cf26808bdb2/nihms180886f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b31d/3579512/436e838e8b88/nihms180886f4.jpg

相似文献

1
PI(3,4,5)P3 and PI(4,5)P2 lipids target proteins with polybasic clusters to the plasma membrane.磷脂酰肌醇-3,4,5-三磷酸（PI(3,4,5)P3）和磷脂酰肌醇-4,5-二磷酸（PI(4,5)P2）脂质通过多碱性簇将蛋白质靶向到质膜。
Science. 2006 Dec 1;314(5804):1458-61. doi: 10.1126/science.1134389. Epub 2006 Nov 9.
2
Lipid products of phosphoinositide 3-kinase interact with Rac1 GTPase and stimulate GDP dissociation.磷脂酰肌醇3激酶的脂质产物与Rac1 GTP酶相互作用并刺激GDP解离。
J Biol Chem. 1998 Nov 13;273(46):30279-86. doi: 10.1074/jbc.273.46.30279.
3
RAB-10-GTPase-mediated regulation of endosomal phosphatidylinositol-4,5-bisphosphate.RAB-10-GTPase 介导的内体磷脂酰肌醇-4,5-二磷酸调节。
Proc Natl Acad Sci U S A. 2012 Aug 28;109(35):E2306-15. doi: 10.1073/pnas.1205278109. Epub 2012 Aug 6.
4
Interactions between Rab and Arf GTPases regulate endosomal phosphatidylinositol-4,5-bisphosphate during endocytic recycling.Rab与Arf GTP酶之间的相互作用在内吞循环过程中调节内体磷脂酰肌醇-4,5-二磷酸。
Small GTPases. 2013 Apr-Jun;4(2):106-9. doi: 10.4161/sgtp.23477. Epub 2013 Feb 7.
5
Cell biology. Tools to tamper with phosphoinositides.细胞生物学。用于干预磷酸肌醇的工具。
Science. 2006 Dec 1;314(5804):1402-3. doi: 10.1126/science.1136314. Epub 2006 Nov 9.
6
Differential roles of phosphatidylserine, PtdIns(4,5)P2, and PtdIns(3,4,5)P3 in plasma membrane targeting of C2 domains. Molecular dynamics simulation, membrane binding, and cell translocation studies of the PKCalpha C2 domain.磷脂酰丝氨酸、磷脂酰肌醇-4,5-二磷酸和磷脂酰肌醇-3,4,5-三磷酸在C2结构域质膜靶向中的不同作用。蛋白激酶Cα C2结构域的分子动力学模拟、膜结合及细胞转位研究。
J Biol Chem. 2008 Sep 19;283(38):26047-58. doi: 10.1074/jbc.M802617200. Epub 2008 Jul 11.
7
PI3K class IB pathway in neutrophils.中性粒细胞中的I类磷脂酰肌醇-3激酶信号通路
Sci STKE. 2007 Oct 9;2007(407):cm3. doi: 10.1126/stke.4072007cm3.
8
PI4P and PI(4,5)P2 are essential but independent lipid determinants of membrane identity.PI4P 和 PI(4,5)P2 是膜特性的必需但独立的脂质决定因素。
Science. 2012 Aug 10;337(6095):727-30. doi: 10.1126/science.1222483. Epub 2012 Jun 21.
9
Regulation of podosomes by integrin alphavbeta3 and Rho GTPase-facilitated phosphoinositide signaling.整合素αvβ3和Rho GTP酶促进的磷酸肌醇信号传导对足体的调控
Eur J Cell Biol. 2006 Apr;85(3-4):311-7. doi: 10.1016/j.ejcb.2006.01.008. Epub 2006 Feb 7.
10
Membrane binding and subcellular localization of retroviral Gag proteins are differentially regulated by MA interactions with phosphatidylinositol-(4,5)-bisphosphate and RNA.逆转录病毒Gag蛋白的膜结合和亚细胞定位受基质蛋白（MA）与磷脂酰肌醇-（4,5）-二磷酸及RNA的相互作用差异调节。
mBio. 2014 Dec 9;5(6):e02202. doi: 10.1128/mBio.02202-14.

引用本文的文献

1
Barley resistance and susceptibility to fungal cell entry involve the interplay of ROP signaling with phosphatidylinositol-monophosphates.大麦对真菌细胞进入的抗性和易感性涉及ROP信号传导与磷脂酰肌醇单磷酸之间的相互作用。
Plant J. 2025 Jul;123(2):e70356. doi: 10.1111/tpj.70356.
2
Optogenetic storage and release of protein and mRNA in live cells and animals.活细胞和动物中蛋白质与信使核糖核酸的光遗传学存储与释放
Nat Commun. 2025 Jul 7;16(1):6230. doi: 10.1038/s41467-025-61322-y.
3
Modulation of host Rab GTPases by Salmonella: mechanisms of immune evasion and intracellular replication.

本文引用的文献

1
Rapid chemically induced changes of PtdIns(4,5)P2 gate KCNQ ion channels.化学诱导下磷脂酰肌醇 -4,5- 二磷酸（PtdIns(4,5)P2）对钾离子通道（KCNQ）的快速变化
Science. 2006 Dec 1;314(5804):1454-7. doi: 10.1126/science.1131163. Epub 2006 Sep 21.
2
Plasma membrane phosphoinositide organization by protein electrostatics.通过蛋白质静电作用实现的质膜磷酸肌醇组织
Nature. 2005 Dec 1;438(7068):605-11. doi: 10.1038/nature04398.
3
LY294002 and LY303511 sensitize tumor cells to drug-induced apoptosis via intracellular hydrogen peroxide production independent of the phosphoinositide 3-kinase-Akt pathway.
沙门氏菌对宿主Rab GTP酶的调控：免疫逃避和细胞内复制机制
Mol Biol Rep. 2025 Apr 30;52(1):440. doi: 10.1007/s11033-025-10547-7.
4
Emerging Approaches for Studying Lipid Dynamics, Metabolism, and Interactions in Cells.研究细胞中脂质动力学、代谢及相互作用的新兴方法
Annu Rev Biochem. 2025 Jun;94(1):417-446. doi: 10.1146/annurev-biochem-083024-110827. Epub 2025 Mar 18.
5
Topology-driven discovery of transmembrane protein S-palmitoylation.拓扑结构驱动的跨膜蛋白S-棕榈酰化修饰发现
J Biol Chem. 2025 Mar;301(3):108259. doi: 10.1016/j.jbc.2025.108259. Epub 2025 Feb 3.
6
A temperature-inducible protein module for control of mammalian cell fate.用于控制哺乳动物细胞命运的温度诱导蛋白模块。
Nat Methods. 2025 Mar;22(3):539-549. doi: 10.1038/s41592-024-02572-4. Epub 2025 Jan 23.
7
Small GTPase ARL4C Associated with Various Cancers Affects Microtubule Nucleation.与多种癌症相关的小GTP酶ARL4C影响微管成核。
Biomedicines. 2024 Dec 18;12(12):2872. doi: 10.3390/biomedicines12122872.
8
Invasion of glioma cells through confined space requires membrane tension regulation and mechano-electrical coupling via Plexin-B2.胶质瘤细胞通过受限空间的侵袭需要通过丛状蛋白-B2调节膜张力和机械-电耦合。
Nat Commun. 2025 Jan 2;16(1):272. doi: 10.1038/s41467-024-55056-6.
9
HIV-1 budding requires cortical actin disassembly by the oxidoreductase MICAL1.HIV-1 出芽需要氧化还原酶 MICAL1 使皮质肌动蛋白解体。
Proc Natl Acad Sci U S A. 2024 Nov 26;121(48):e2407835121. doi: 10.1073/pnas.2407835121. Epub 2024 Nov 18.
10
Regulation of BCR-dependent germinal center B-cell formation by HGAL and insight into its emerging myeloid ortholog, C1ORF150.BCR 依赖性生发中心 B 细胞形成的调控因子 HGAL 及其新兴的髓系同源物 C1ORF150 的研究进展。
Front Immunol. 2024 Oct 15;15:1437516. doi: 10.3389/fimmu.2024.1437516. eCollection 2024.
LY294002和LY303511通过细胞内过氧化氢生成使肿瘤细胞对药物诱导的凋亡敏感，且不依赖于磷酸肌醇3激酶 - Akt途径。
Cancer Res. 2005 Jul 15;65(14):6264-74. doi: 10.1158/0008-5472.CAN-05-0152.
4
An inducible translocation strategy to rapidly activate and inhibit small GTPase signaling pathways.一种用于快速激活和抑制小GTP酶信号通路的诱导性易位策略。
Nat Methods. 2005 Jun;2(6):415-8. doi: 10.1038/nmeth763.
5
An acylation cycle regulates localization and activity of palmitoylated Ras isoforms.酰化循环调节棕榈酰化Ras亚型的定位和活性。
Science. 2005 Mar 18;307(5716):1746-52. doi: 10.1126/science.1105654. Epub 2005 Feb 10.
6
Controlling the location and activation of Rab GTPases.控制Rab GTP酶的定位与激活。
Curr Opin Cell Biol. 2004 Aug;16(4):451-7. doi: 10.1016/j.ceb.2004.06.014.
7
Cell biology. Integrins, rafts, Rac, and Rho.细胞生物学。整合素、脂筏、Rac和Rho。
Science. 2004 Feb 6;303(5659):773-4. doi: 10.1126/science.1094376.
8
Specific localization and timing in neuronal signal transduction mediated by protein-lipid interactions.由蛋白质-脂质相互作用介导的神经元信号转导中的特定定位和时间安排。
Neuron. 2003 Oct 9;40(2):319-30. doi: 10.1016/s0896-6273(03)00634-2.
9
Switch-of-function mutants based on morphology classification of Ras superfamily small GTPases.基于Ras超家族小GTP酶形态学分类的功能转换突变体
Cell. 2003 May 2;113(3):315-28. doi: 10.1016/s0092-8674(03)00315-5.
10
PIP(2) and proteins: interactions, organization, and information flow.磷脂酰肌醇-4,5-二磷酸（PIP(2)）与蛋白质：相互作用、组织及信息流
Annu Rev Biophys Biomol Struct. 2002;31:151-75. doi: 10.1146/annurev.biophys.31.082901.134259. Epub 2001 Oct 25.