干扰素作用机制：PKR（干扰素诱导的RNA依赖性蛋白激酶）分子间自磷酸化的特性
Mechanism of interferon action: characterization of the intermolecular autophosphorylation of PKR, the interferon-inducible, RNA-dependent protein kinase.
作者信息
Thomis D C, Samuel C E
机构信息
Department of Biological Sciences, University of California, Santa Barbara 93106, USA.
出版信息
J Virol. 1995 Aug;69(8):5195-8. doi: 10.1128/JVI.69.8.5195-5198.1995.
Abstract
The interferon-inducible, RNA-dependent protein kinase (PKR) is activated by autophosphorylation, a process mediated by double-stranded RNA. A catalytically deficient, histidine-tagged mutant PKR protein [His-PKR(K296R)] was used as the substrate for characterization of the intermolecular phosphorylation catalyzed by purified wild-type PKR [PKR(Wt)]. The intermolecular autophosphorylation of His-PKR(K296R) by PKR(Wt) was RNA dependent. Excess His-PKR(K296R) substrate inhibited both the auto- and the trans-phosphorylation activities of PKR(Wt). Inhibition of PKR(Wt) by His-PKR(K296R) was relieved by higher concentrations of activator double-stranded RNA. Phosphopeptide analysis revealed that the sites of intermolecular autophosphorylation in His-PKR(K296R) were very similar, if not identical, to the sites that were autophosphorylated in PKR(Wt) and suggest a multiple of four major phosphorylation sites per PKR molecule.
摘要
干扰素诱导的RNA依赖性蛋白激酶（PKR）通过自身磷酸化被激活，这一过程由双链RNA介导。一种催化缺陷的、带有组氨酸标签的突变型PKR蛋白[His-PKR(K296R)]被用作底物，以表征纯化的野生型PKR[PKR(Wt)]催化的分子间磷酸化。PKR(Wt)对His-PKR(K296R)的分子间自身磷酸化是RNA依赖性的。过量的His-PKR(K296R)底物抑制了PKR(Wt)的自身磷酸化和转磷酸化活性。更高浓度的激活剂双链RNA可解除His-PKR(K296R)对PKR(Wt)的抑制。磷酸肽分析表明，His-PKR(K296R)分子间自身磷酸化的位点与PKR(Wt)自身磷酸化的位点非常相似（如果不是完全相同的话），这表明每个PKR分子有多个四个主要磷酸化位点。
相似文献
1
Mechanism of interferon action: characterization of the intermolecular autophosphorylation of PKR, the interferon-inducible, RNA-dependent protein kinase.干扰素作用机制：PKR（干扰素诱导的RNA依赖性蛋白激酶）分子间自磷酸化的特性
J Virol. 1995 Aug;69(8):5195-8. doi: 10.1128/JVI.69.8.5195-5198.1995.
2
Mechanism of interferon action. Biochemical and genetic evidence for the intermolecular association of the RNA-dependent protein kinase PKR from human cells.干扰素作用机制。来自人类细胞的RNA依赖性蛋白激酶PKR分子间缔合的生化与遗传学证据。
Virology. 1996 Jan 1;215(1):31-9. doi: 10.1006/viro.1996.0004.
3
Mechanism of interferon action: evidence for intermolecular autophosphorylation and autoactivation of the interferon-induced, RNA-dependent protein kinase PKR.干扰素作用机制：干扰素诱导的RNA依赖性蛋白激酶PKR分子间自磷酸化和自激活的证据
J Virol. 1993 Dec;67(12):7695-700. doi: 10.1128/JVI.67.12.7695-7700.1993.
4
Characterization of the heparin-mediated activation of PKR, the interferon-inducible RNA-dependent protein kinase.肝素介导的PKR（干扰素诱导的RNA依赖性蛋白激酶）激活的特征分析。
Virology. 1996 Jul 1;221(1):180-8. doi: 10.1006/viro.1996.0364.
5
Autophosphorylation sites participate in the activation of the double-stranded-RNA-activated protein kinase PKR.自磷酸化位点参与双链RNA激活蛋白激酶PKR的激活过程。
Mol Cell Biol. 1996 Nov;16(11):6295-302. doi: 10.1128/MCB.16.11.6295.
6
Mechanism of interferon action: autoregulation of RNA-dependent P1/eIF-2 alpha protein kinase (PKR) expression in transfected mammalian cells.干扰素作用机制：转染哺乳动物细胞中RNA依赖性P1/eIF-2α蛋白激酶（PKR）表达的自动调节
Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10837-41. doi: 10.1073/pnas.89.22.10837.
7
Regulation of the interferon-inducible protein kinase PKR and (2'-5')oligo(adenylate) synthetase by a catalytically inactive PKR mutant through competition for double-stranded RNA binding.通过与双链RNA结合的竞争，催化失活的PKR突变体对干扰素诱导蛋白激酶PKR和（2'-5'）寡腺苷酸合成酶的调节。
Eur J Biochem. 1995 May 15;230(1):97-103. doi: 10.1111/j.1432-1033.1995.0097i.x.
8
Mechanism of interferon action: RNA-binding activity of full-length and R-domain forms of the RNA-dependent protein kinase PKR--determination of KD values for VAI and TAR RNAs.干扰素作用机制：RNA 依赖性蛋白激酶 PKR 的全长及 R 结构域形式的 RNA 结合活性——VAI 和 TAR RNA 的 KD 值测定
Virology. 1995 Jan 10;206(1):511-9. doi: 10.1016/s0042-6822(95)80067-0.
9
The P58 cellular inhibitor complexes with the interferon-induced, double-stranded RNA-dependent protein kinase, PKR, to regulate its autophosphorylation and activity.P58细胞抑制剂与干扰素诱导的双链RNA依赖性蛋白激酶PKR形成复合物，以调节其自身磷酸化和活性。
J Biol Chem. 1996 Jan 19;271(3):1702-7. doi: 10.1074/jbc.271.3.1702.
10
The 58,000-dalton cellular inhibitor of the interferon-induced double-stranded RNA-activated protein kinase (PKR) is a member of the tetratricopeptide repeat family of proteins.干扰素诱导的双链RNA激活蛋白激酶（PKR）的58,000道尔顿细胞抑制剂是四肽重复序列蛋白家族的成员。
Mol Cell Biol. 1994 Apr;14(4):2331-42. doi: 10.1128/mcb.14.4.2331-2342.1994.
引用本文的文献
1
Structural Basis of Protein Kinase R Autophosphorylation.蛋白激酶 R 自身磷酸化的结构基础。
Biochemistry. 2019 Jul 9;58(27):2967-2977. doi: 10.1021/acs.biochem.9b00161. Epub 2019 Jun 27.
2
Activation of SsoPK4, an Archaeal eIF2α Kinase Homolog, by Oxidized CoA.氧化型辅酶A对古菌eIF2α激酶同源物SsoPK4的激活作用。
Proteomes. 2015 May 15;3(2):89-116. doi: 10.3390/proteomes3020089.
3
Editing of Cellular Self-RNAs by Adenosine Deaminase ADAR1 Suppresses Innate Immune Stress Responses.腺苷脱氨酶ADAR1对细胞自身RNA的编辑可抑制先天性免疫应激反应。
J Biol Chem. 2016 Mar 18;291(12):6158-68. doi: 10.1074/jbc.M115.709014. Epub 2016 Jan 27.
4
Positional effect of phosphorylation sites 266 and 267 in the cytoplasmic domain of the E2 protein of hepatitis C virus 3a genotype: interferon resistance analysis via sequence alignment.丙型肝炎病毒 3a 基因型 E2 蛋白胞质域中磷酸化位点 266 和 267 的位置效应：通过序列比对进行干扰素耐药性分析。
Virol J. 2011 May 5;8:204. doi: 10.1186/1743-422X-8-204.
5
The structure of the PERK kinase domain suggests the mechanism for its activation.PERK激酶结构域的结构揭示了其激活机制。
Acta Crystallogr D Biol Crystallogr. 2011 May;67(Pt 5):423-8. doi: 10.1107/S0907444911006445. Epub 2011 Apr 13.
6
Innate immune evasion mediated by the Ambystoma tigrinum virus eukaryotic translation initiation factor 2alpha homologue.美洲大鲵病毒真核翻译起始因子 2alpha 同源物介导的固有免疫逃避。
J Virol. 2011 May;85(10):5061-9. doi: 10.1128/JVI.01488-10. Epub 2011 Mar 9.
7
Molecular basis for an attenuated cytoplasmic dsRNA response in human embryonic stem cells.人胚胎干细胞中细胞质 dsRNA 反应减弱的分子基础。
Cell Cycle. 2010 Sep 1;9(17):3552-64. doi: 10.4161/cc.9.17.12792. Epub 2010 Sep 24.
8
Protein kinase PKR-dependent activation of mitogen-activated protein kinases occurs through mitochondrial adapter IPS-1 and is antagonized by vaccinia virus E3L.依赖蛋白激酶PKR的丝裂原活化蛋白激酶激活通过线粒体衔接蛋白IPS-1发生，并受到痘苗病毒E3L的拮抗。
J Virol. 2009 Jun;83(11):5718-25. doi: 10.1128/JVI.00224-09. Epub 2009 Mar 25.
9
Specific inhibition of the PKR-mediated antiviral response by the murine cytomegalovirus proteins m142 and m143.小鼠巨细胞病毒蛋白m142和m143对PKR介导的抗病毒反应的特异性抑制作用。
J Virol. 2009 Feb;83(3):1260-70. doi: 10.1128/JVI.01558-08. Epub 2008 Nov 19.
10
Stimulation of Ebola virus production from persistent infection through activation of the Ras/MAPK pathway.通过激活Ras/丝裂原活化蛋白激酶（MAPK）途径刺激持续性感染中的埃博拉病毒产生。
Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17982-7. doi: 10.1073/pnas.0809698105. Epub 2008 Nov 3.
本文引用的文献
1
Translational regulation by the interferon-induced double-stranded-RNA-activated 68-kDa protein kinase.干扰素诱导的双链RNA激活的68 kDa蛋白激酶介导的翻译调控
Proc Natl Acad Sci U S A. 1993 May 15;90(10):4621-5. doi: 10.1073/pnas.90.10.4621.
2
The eIF-2 alpha protein kinases, regulators of translation in eukaryotes from yeasts to humans.真核生物中从酵母到人类的翻译调控因子——真核起始因子2α蛋白激酶。
J Biol Chem. 1993 Apr 15;268(11):7603-6.
3
Mechanism of interferon action: structure of the mouse PKR gene encoding the interferon-inducible RNA-dependent protein kinase.
Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):7995-9. doi: 10.1073/pnas.91.17.7995.
4
Mechanism of interferon action: evidence for intermolecular autophosphorylation and autoactivation of the interferon-induced, RNA-dependent protein kinase PKR.干扰素作用机制：干扰素诱导的RNA依赖性蛋白激酶PKR分子间自磷酸化和自激活的证据
J Virol. 1993 Dec;67(12):7695-700. doi: 10.1128/JVI.67.12.7695-7700.1993.
5
Reversal of the interferon-sensitive phenotype of a vaccinia virus lacking E3L by expression of the reovirus S4 gene.通过呼肠孤病毒S4基因的表达逆转缺乏E3L的痘苗病毒的干扰素敏感表型。
J Virol. 1995 Jan;69(1):499-505. doi: 10.1128/JVI.69.1.499-505.1995.
6
Mechanism of interferon action. Translational control and the RNA-dependent protein kinase (PKR): antagonists of PKR enhance the translational activity of mRNAs that include a 161 nucleotide region from reovirus S1 mRNA.干扰素作用机制。翻译控制与RNA依赖性蛋白激酶（PKR）：PKR的拮抗剂可增强包含呼肠孤病毒S1 mRNA中161个核苷酸区域的mRNA的翻译活性。
J Biol Regul Homeost Agents. 1994 Jan-Mar;8(1):15-24.
7
Mechanism of interferon action motif I of the interferon-induced, RNA-dependent protein kinase (PKR) is sufficient to mediate RNA-binding activity.干扰素诱导的RNA依赖性蛋白激酶（PKR）的干扰素作用基序I的机制足以介导RNA结合活性。
Virology. 1994 Jan;198(1):92-9. doi: 10.1006/viro.1994.1011.
8
Further characterization of the protein kinase activity mediated by interferon in mouse and human cells.对干扰素在小鼠和人类细胞中介导的蛋白激酶活性的进一步表征。
J Biol Chem. 1984 Jul 10;259(13):8494-8.
9
10
Inhibition of mRNA binding to ribosomes by localized activation of dsRNA-dependent protein kinase.通过双链RNA依赖性蛋白激酶的局部激活抑制信使核糖核酸与核糖体的结合。
Nature. 1984;311(5981):79-81. doi: 10.1038/311079a0.
Zotero 插件